Advertisement
Journal of Investigative Dermatology Home

Mechanisms of Photosensitivity in Autoimmunity

  • Author Footnotes
    4 These authors contributed equally to this work.
    Shannon N. Estadt
    Footnotes
    4 These authors contributed equally to this work.
    Affiliations
    Division of Rheumatology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Graduate Program in Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA
    Search for articles by this author
  • Author Footnotes
    4 These authors contributed equally to this work.
    Mitra P. Maz
    Footnotes
    4 These authors contributed equally to this work.
    Affiliations
    Division of Rheumatology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Graduate Program in Immunology, Medical School, University of Michigan, Ann Arbor, Michigan, USA
    Search for articles by this author
  • Jon Musai
    Affiliations
    Division of Rheumatology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Search for articles by this author
  • J. Michelle Kahlenberg
    Correspondence
    Correspondence: J. Michelle Kahlenberg, Division of Rheumatology, Department of Internal Medicine, Michigan Medicine, University of Michigan, 5570A MSRB II, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-5678, USA.
    Affiliations
    Division of Rheumatology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
    Search for articles by this author
  • Author Footnotes
    4 These authors contributed equally to this work.
      Aberrant responses to UV light frequently lead to the formation of skin lesions and the activation of systemic inflammation in some autoimmune diseases, especially systemic lupus erythematosus. Whereas the effects of UV light on the skin have been studied for decades, only recently have some of the mechanisms that contribute to abnormal responses to UV light in patients with autoimmune diseases been uncovered. This review will discuss the biology of UV in the epidermis and discuss the abnormal epidermal and inflammatory mechanisms that contribute to photosensitivity. Further research is required to fully understand how to normalize UV-mediated inflammation in patients with autoimmune diseases.

      Abbreviations:

      8-OHdG (8-hydroxy-2′-deoxyguanosine), AE (annular erythema), cGAMP (cyclic guanosine monophosphate–adenosine monophosphate), cGAS (cyclic guanosine monophosphate–adenosine monophosphate synthase), CLE (cutaneous lupus erythematosus), CPD (cyclobutane pyrimidine dimer), DC (dendritic cell), DM (dermatomyositis), KC (keratinocyte), LC (Langerhans cell), MMP (matrix metalloproteinase), NET (neutrophil extracellular trap), pDC (plasmacytoid dendritic cell), SLE (systemic lupus erythematosus), SS (Sjögren’s syndrome), Th (T helper), TLR (toll-like receptor), Treg (regulatory T cell), WT (wild type)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      PDF Download and 24 Hours Online Access
      Society Members (SID/ESDR), remember to log in for access.

      Subscribe:

      Subscribe to Journal of Investigative Dermatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Abe T.
        • Barber G.N.
        Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-κB activation through TBK1.
        J Virol. 2014; 88: 5328-5341
        • Ablasser A.
        • Goldeck M.
        • Cavlar T.
        • Deimling T.
        • Witte G.
        • Röhl I.
        • et al.
        cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING.
        Nature. 2013; 498: 380-384
        • Apel F.
        • Andreeva L.
        • Knackstedt L.S.
        • Streeck R.
        • Frese C.K.
        • Goosmann C.
        • et al.
        The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps.
        Sci Signal. 2021; 14eaax7942
        • Avalos-Díaz E.
        • Alvarado-Flores E.
        • Herrera-Esparza R.
        UV-A irradiation induces transcription of IL-6 and TNF alpha genes in human keratinocytes and dermal fibroblasts.
        Rev Rhum Engl Ed. 1999; 66: 13-19
        • Barber G.N.
        STING: infection, inflammation and cancer.
        Nat Rev Immunol. 2015; 15: 760-770
        • Barrat F.J.
        • Meeker T.
        • Gregorio J.
        • Chan J.H.
        • Uematsu S.
        • Akira S.
        • et al.
        Nucleic acids of mammalian origin can act as endogenous ligands for toll-like receptors and may promote systemic lupus erythematosus.
        J Exp Med. 2005; 202: 1131-1139
        • Bashir M.M.
        • Sharma M.R.
        • Werth V.P.
        UVB and proinflammatory cytokines synergistically activate TNF-alpha production in keratinocytes through enhanced gene transcription.
        J Invest Dermatol. 2009; 129: 994-1001
        • Batista L.F.Z.
        • Kaina B.
        • Meneghini R.
        • Menck C.F.M.
        How DNA lesions are turned into powerful killing structures: insights from UV-induced apoptosis.
        Mutat Res. 2009; 681: 197-208
        • Berggren O.
        • Hagberg N.
        • Alexsson A.
        • Weber G.
        • Rönnblom L.
        • Eloranta M.L.
        Plasmacytoid dendritic cells and RNA-containing immune complexes drive expansion of peripheral B cell subsets with an SLE-like phenotype.
        PLoS One. 2017; 12e0183946
        • Bernard J.J.
        • Cowing-Zitron C.
        • Nakatsuji T.
        • Muehleisen B.
        • Muto J.
        • Borkowski A.W.
        • et al.
        Ultraviolet radiation damages self noncoding RNA and is detected by TLR3.
        Nat Med. 2012; 18: 1286-1290
        • Berthier C.C.
        • Tsoi L.C.
        • Reed T.J.
        • Stannard J.N.
        • Myers E.M.
        • Namas R.
        • et al.
        Molecular profiling of cutaneous lupus lesions identifies subgroups distinct from clinical phenotypes.
        J Clin Med. 2019; 8: 1244
        • Bijl M.
        • Reefman E.
        • Horst G.
        • Limburg P.C.
        • Kallenberg C.G.
        Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement.
        Ann Rheum Dis. 2006; 65: 57-63
        • Brink N.
        • Szamel M.
        • Young A.R.
        • Wittern K.P.
        • Bergemann J.
        Comparative quantification of IL-1beta, IL-10, IL-10r, TNFalpha and IL-7 mRNA levels in UV-irradiated human skin in vivo.
        Inflamm Res. 2000; 49: 290-296
        • Brito-Zerón P.
        • Retamozo S.
        • Akasbi M.
        • Gandía M.
        • Perez-De-Lis M.
        • Soto-Cardenas M.J.
        • et al.
        Annular erythema in primary Sjogren's syndrome: description of 43 non-Asian cases.
        Lupus. 2014; 23: 166-175
        • Bruhs A.
        • Schwarz T.
        Ultraviolet radiation-induced immunosuppression: induction of regulatory T cells.
        Methods Mol Biol. 2017; 1559: 63-73
        • Burd C.J.
        • Kinyamu H.K.
        • Miller F.W.
        • Archer T.K.
        UV radiation regulates Mi-2 through protein translation and stability.
        J Biol Chem. 2008; 283: 34976-34982
        • Byrne S.N.
        • Halliday G.M.
        B cells activated in lymph nodes in response to ultraviolet irradiation or by interleukin-10 inhibit dendritic cell induction of immunity.
        J Invest Dermatol. 2005; 124: 570-578
        • Caricchio R.
        • McPhie L.
        • Cohen P.L.
        Ultraviolet B radiation-induced cell death: critical role of ultraviolet dose in inflammation and lupus autoantigen redistribution.
        J Immunol. 2003; 171: 5778-5786
        • Casciola-Rosen L.A.
        • Anhalt G.
        • Rosen A.
        Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes.
        J Exp Med. 1994; 179: 1317-1330
        • Cassius C.
        • Amode R.
        • Delord M.
        • Battistella M.
        • Poirot J.
        • How-Kit A.
        • et al.
        MDA5+ dermatomyositis is associated with stronger skin type I interferon transcriptomic signature with upregulation of IFN-κ transcript.
        J Invest Dermatol. 2020; 140: 1276-1279.e7
        • Cela E.M.
        • Friedrich A.
        • Paz M.L.
        • Vanzulli S.I.
        • Leoni J.
        • González Maglio D.H.
        Time-course study of different innate immune mediators produced by UV-irradiated skin: comparative effects of short and daily versus a single harmful UV exposure.
        Immunology. 2015; 145: 82-93
        • Chen H.H.
        • Tsai L.J.
        • Lee K.R.
        • Chen Y.M.
        • Hung W.T.
        • Chen D.Y.
        Genetic association of complement component 2 polymorphism with systemic lupus erythematosus.
        Tissue Antigens. 2015; 86: 122-133
        • Clingen P.H.
        • Berneburg M.
        • Petit-Frère C.
        • Woollons A.
        • Lowe J.E.
        • Arlett C.F.
        • et al.
        Contrasting effects of an ultraviolet B and an ultraviolet A tanning lamp on interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1 expression.
        Br J Dermatol. 2001; 145: 54-62
        • Dall'Era M.
        • Pauli M.L.
        • Remedios K.
        • Taravati K.
        • Sandova P.M.
        • Putnam A.L.
        • et al.
        Adoptive Treg cell therapy in a patient with systemic lupus erythematosus.
        Arthritis Rheumatol. 2019; 71: 431-440
        • De Groof A.
        • Ducreux J.
        • Vidal-Bralo L.
        • Tyteca D.
        • Galant C.
        • Marot L.
        • et al.
        Toll-like receptor 3 increases antigen-presenting cell responses to a pro-apoptotic stimulus, yet does not contribute to systemic lupus erythematosus genetic susceptibility.
        Clin Exp Rheumatol. 2020; 38: 881-890
        • Debes G.F.
        • McGettigan S.E.
        Skin-associated B cells in health and inflammation.
        J Immunol. 2019; 202: 1659-1666
        • Denny M.F.
        • Yalavarthi S.
        • Zhao W.
        • Thacker S.G.
        • Anderson M.
        • Sandy A.R.
        • et al.
        A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs [published correction appears in J Immunol 2010;185:3779].
        J Immunol. 2010; 184: 3284-3297
        • Der E.
        • Suryawanshi H.
        • Morozov P.
        • Kustagi M.
        • Goilav B.
        • Ranabothu S.
        • et al.
        Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways [published correction appears in Nat Immunol 2019;20:1556].
        Nat Immunol. 2019; 20: 915-927
        • Di Nuzzo S.
        • de Rie M.A.
        • van der Loos C.M.
        • Bos J.D.
        • Teunissen M.B.
        Solar-simulated ultraviolet irradiation induces selective influx of CD4+ T lymphocytes in normal human skin.
        Photochem Photobiol. 1996; 64: 988-993
        • Dourmishev L.
        • Meffert H.
        • Piazena H.
        Dermatomyositis: comparative studies of cutaneous photosensitivity in lupus erythematosus and normal subjects.
        Photodermatol Photoimmunol Photomed. 2004; 20: 230-234
        • El-Abaseri T.B.
        • Putta S.
        • Hansen L.A.
        Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor.
        Carcinogenesis. 2006; 27: 225-231
        • Elmore S.
        Apoptosis: a review of programmed cell death.
        Toxicol Pathol. 2007; 35: 495-516
        • Ertugrul G.
        • Keles D.
        • Oktay G.
        • Aktan S.
        Matrix metalloproteinase-2 and -9 activity levels increase in cutaneous lupus erythematosus lesions and correlate with disease severity.
        Arch Dermatol Res. 2018; 310: 173-179
        • Fabré V.C.
        • Lear S.
        • Reichlin M.
        • Hodge S.J.
        • Callen J.P.
        Twenty percent of biopsy specimens from sun-exposed skin of normal young adults demonstrate positive immunofluorescence.
        Arch Dermatol. 1991; 127: 1006-1011
        • Fisher G.J.
        • Choi H.C.
        • Bata-Csorgo Z.
        • Shao Y.
        • Datta S.
        • Wang Z.Q.
        • et al.
        Ultraviolet irradiation increases matrix metalloproteinase-8 protein in human skin in vivo.
        J Invest Dermatol. 2001; 117: 219-226
        • Fitzgerald K.A.
        • McWhirter S.M.
        • Faia K.L.
        • Rowe D.C.
        • Latz E.
        • Golenbock D.T.
        • et al.
        IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
        Nat Immunol. 2003; 4: 491-496
        • Franz B.
        • Fritzsching B.
        • Riehl A.
        • Oberle N.
        • Klemke C.D.
        • Sykora J.
        • et al.
        Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus.
        Arthritis Rheum. 2007; 56: 1910-1920
        • Fredi M.
        • Cavazzana I.
        • Quinzanini M.
        • Taraborelli M.
        • Cartella S.
        • Tincani A.
        • et al.
        Rare autoantibodies to cellular antigens in systemic lupus erythematosus.
        Lupus. 2014; 23: 672-677
        • Furukawa F.
        • Kashihara-Sawami M.
        • Lyons M.B.
        • Norris D.A.
        Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): implications for the pathogenesis of photosensitive cutaneous lupus.
        J Invest Dermatol. 1990; 94: 77-85
        • Gehrke N.
        • Mertens C.
        • Zillinger T.
        • Wenzel J.
        • Bald T.
        • Zahn S.
        • et al.
        Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing.
        Immunity. 2013; 39: 482-495
        • Gerli R.
        • Caponi L.
        • Tincani A.
        • Scorza R.
        • Sabbadini M.G.
        • Danieli M.G.
        • et al.
        Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients.
        Rheumatology (Oxford). 2002; 41: 1357-1366
        • Golan T.D.
        • Elkon K.B.
        • Gharavi A.E.
        • Krueger J.G.
        Enhanced membrane binding of autoantibodies to cultured keratinocytes of systemic lupus erythematosus patients after ultraviolet B/ultraviolet A irradiation.
        J Clin Invest. 1992; 90: 1067-1076
        • Günther C.
        • Kind B.
        • Reijns M.A.
        • Berndt N.
        • Martinez-Bueno M.
        • Wolf C.
        • et al.
        Defective removal of ribonucleotides from DNA promotes systemic autoimmunity.
        J Clin Invest. 2015; 125: 413-424
        • Han X.
        • Vesely M.D.
        • Yang W.
        • Sanmamed M.F.
        • Badri T.
        • Alawa J.
        • et al.
        PD-1H (VISTA)-mediated suppression of autoimmunity in systemic and cutaneous lupus erythematosus.
        Sci Transl Med. 2019; 11eaax1159
        • Harding S.M.
        • Benci J.L.
        • Irianto J.
        • Discher D.E.
        • Minn A.J.
        • Greenberg R.A.
        Mitotic progression following DNA damage enables pattern recognition within micronuclei.
        Nature. 2017; 548: 466-470
        • Hasan T.
        • Nyberg F.
        • Stephansson E.
        • Puska P.
        • Häkkinen M.
        • Sarna S.
        • et al.
        Photosensitivity in lupus erythematosus, UV photoprovocation results compared with history of photosensitivity and clinical findings.
        Br J Dermatol. 1997; 136: 699-705
        • Hatakeyama M.
        • Fukunaga A.
        • Washio K.
        • Taguchi K.
        • Oda Y.
        • Ogura K.
        • et al.
        Anti-inflammatory role of Langerhans cells and apoptotic keratinocytes in ultraviolet-B-induced cutaneous inflammation.
        J Immunol. 2017; 199: 2937-2947
        • Hawk J.L.
        • Murphy G.M.
        • Holden C.A.
        The presence of neutrophils in human cutaneous ultraviolet-B inflammation.
        Br J Dermatol. 1988; 118: 27-30
        • He J.
        • Zhang R.
        • Shao M.
        • Zhao X.
        • Miao M.
        • Chen J.
        • et al.
        Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial.
        Ann Rheum Dis. 2020; 79: 141-149
        • Hildesheim J.
        • Bulavin D.V.
        • Anver M.R.
        • Alvord W.G.
        • Hollander M.C.
        • Vardanian L.
        • et al.
        Gadd45a protects against UV irradiation-induced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53.
        Cancer Res. 2002; 62: 7305-7315
        • Homey B.
        • Alenius H.
        • Müller A.
        • Soto H.
        • Bowman E.P.
        • Yuan W.
        • et al.
        CCL27-CCR10 interactions regulate T cell-mediated skin inflammation.
        Nat Med. 2002; 8: 157-165
        • Hopfner K.P.
        • Hornung V.
        Molecular mechanisms and cellular functions of cGAS-STING signalling.
        Nat Rev Mol Cell Biol. 2020; 21: 501-521
        • Hussein M.R.
        • Aboulhagag N.M.
        • Atta H.S.
        • Atta S.M.
        Evaluation of the profile of the immune cell infiltrate in lichen planus, discoid lupus erythematosus, and chronic dermatitis.
        Pathology. 2008; 40: 682-693
        • Ioannides D.
        • Golden B.D.
        • Buyon J.P.
        • Bystryn J.C.
        Expression of SS-A/Ro and SS-B/La antigens in skin biopsy specimens of patients with photosensitive forms of lupus erythematosus.
        Arch Dermatol. 2000; 136: 340-346
        • Jones S.K.
        Ultraviolet radiation (UVR) induces cell-surface Ro/SSA antigen expression by human keratinocytes in vitro: a possible mechanism for the UVR induction of cutaneous lupus lesions.
        Br J Dermatol. 1992; 126: 546-553
        • Katayama S.
        • Panelius J.
        • Koskenmies S.
        • Skoog T.
        • Mähönen K.
        • Kisand K.
        • et al.
        Delineating the healthy human skin UV response and early induction of interferon pathway in cutaneous lupus erythematosus.
        J Invest Dermatol. 2019; 139: 2058-2061.e4
        • Kemp M.G.
        • Lindsey-Boltz L.A.
        • Sancar A.
        UV light potentiates STING (stimulator of interferon genes)-dependent innate immune signaling through deregulation of ULK1 (Unc51-like kinase 1).
        J Biol Chem. 2015; 290: 12184-12194
        • Kind P.
        • Lehmann P.
        • Plewig G.
        Phototesting in lupus erythematosus.
        J Invest Dermatol. 1993; 100: S53-S57
        • Köck A.
        • Schwarz T.
        • Kirnbauer R.
        • Urbanski A.
        • Perry P.
        • Ansel J.C.
        • et al.
        Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light.
        J Exp Med. 1990; 172: 1609-1614
        • Kripke M.L.
        • Fisher M.S.
        Immunologic parameters of ultraviolet carcinogenesis.
        J Natl Cancer Inst. 1976; 57: 211-215
        • Kuhn A.
        • Herrmann M.
        • Kleber S.
        • Beckmann-Welle M.
        • Fehsel K.
        • Martin-Villalba A.
        • et al.
        Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation.
        Arthritis Rheum. 2006; 54: 939-950
        • Kuhn A.
        • Landmann A.
        The classification and diagnosis of cutaneous lupus erythematosus.
        J Autoimmun. 2014; 48–49: 14-19
        • Lauffer F.
        • Jargosch M.
        • Krause L.
        • Garzorz-Stark N.
        • Franz R.
        • Roenneberg S.
        • et al.
        Type I immune response induces keratinocyte necroptosis and is associated with interface dermatitis.
        J Invest Dermatol. 2018; 138: 1785-1794
        • Lawley W.
        • Doherty A.
        • Denniss S.
        • Chauhan D.
        • Pruijn G.
        • van Venrooij W.J.
        • et al.
        Rapid lupus autoantigen relocalization and reactive oxygen species accumulation following ultraviolet irradiation of human keratinocytes.
        Rheumatology (Oxford). 2000; 39: 253-261
        • Li X.
        • Shu C.
        • Yi G.
        • Chaton C.T.
        • Shelton C.L.
        • Diao J.
        • et al.
        Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization.
        Immunity. 2013; 39: 1019-1031
        • Li X.D.
        • Wu J.
        • Gao D.
        • Wang H.
        • Sun L.
        • Chen Z.J.
        Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects.
        Science. 2013; 341: 1390-1394
        • Liu J.
        • Berthier C.C.
        • Kahlenberg J.M.
        Enhanced inflammasome activity in systemic lupus erythematosus is mediated via type I interferon-induced up-regulation of interferon regulatory factor 1.
        Arthritis Rheumatol. 2017; 69: 1840-1849
        • Mackenzie K.J.
        • Carroll P.
        • Martin C.A.
        • Murina O.
        • Fluteau A.
        • Simpson D.J.
        • et al.
        cGAS surveillance of micronuclei links genome instability to innate immunity.
        Nature. 2017; 548: 461-465
        • MacLeod A.S.
        • Rudolph R.
        • Corriden R.
        • Ye I.
        • Garijo O.
        • Havran W.L.
        Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair.
        J Immunol. 2014; 192: 5695-5702
        • Mamyrova G.
        • Rider L.G.
        • Ehrlich A.
        • Jones O.
        • Pachman L.M.
        • Nickeson R.
        • et al.
        Environmental factors associated with disease flare in juvenile and adult dermatomyositis.
        Rheumatology (Oxford). 2017; 56: 1342-1347
        • McHugh N.
        • James I.
        • Maddison P.
        Clinical significance of antibodies to a 68 kDa U1RNP polypeptide in connective tissue disease.
        J Rheumatol. 1990; 17: 1320-1328
        • Means T.K.
        • Latz E.
        • Hayashi F.
        • Murali M.R.
        • Golenbock D.T.
        • Luster A.D.
        Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9.
        J Clin Invest. 2005; 115: 407-417
        • Meller S.
        • Winterberg F.
        • Gilliet M.
        • Müller A.
        • Lauceviciute I.
        • Rieker J.
        • et al.
        Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: an amplification cycle triggering cutaneous lupus erythematosus.
        Arthritis Rheum. 2005; 52: 1504-1516
        • Menéndez A.
        • Gómez J.
        • Caminal-Montero L.
        • Díaz-López J.B.
        • Cabezas-Rodríguez I.
        • Mozo L.
        Common and specific associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies in systemic lupus erythematosus.
        ScientificWorldJournal. 2013; 2013: 832789
        • Menke J.
        • Hsu M.Y.
        • Byrne K.T.
        • Lucas J.A.
        • Rabacal W.A.
        • Croker B.P.
        • et al.
        Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice.
        J Immunol. 2008; 181: 7367-7379
        • Mond C.B.
        • Peterson M.G.
        • Rothfield N.F.
        Correlation of anti-Ro antibody with photosensitivity rash in systemic lupus erythematosus patients.
        Arthritis Rheum. 1989; 32: 202-204
        • Morales J.
        • Homey B.
        • Vicari A.P.
        • Hudak S.
        • Oldham E.
        • Hedrick J.
        • et al.
        CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells.
        Proc Natl Acad Sci USA. 1999; 96: 14470-14475
        • Motwani M.
        • Pesiridis S.
        • Fitzgerald K.A.
        DNA sensing by the cGAS-STING pathway in health and disease.
        Nat Rev Genet. 2019; 20: 657-674
        • Neubert E.
        • Bach K.M.
        • Busse J.
        • Bogeski I.
        • Schön M.P.
        • Kruss S.
        • et al.
        Blue and long-wave ultraviolet light induce in vitro neutrophil extracellular trap (NET) formation.
        Front Immunol. 2019; 10: 2428
        • O'Brien J.C.
        • Hosler G.A.
        • Chong B.F.
        Changes in T cell and B cell composition in discoid lupus erythematosus skin at different stages.
        J Dermatol Sci. 2017; 85: 247-249
        • Okada S.
        • Weatherhead E.
        • Targoff I.N.
        • Wesley R.
        • Miller F.W.
        • International Myositis Collaborative Study Group
        Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease.
        Arthritis Rheum. 2003; 48: 2285-2293
        • Pablos J.L.
        • Santiago B.
        • Galindo M.
        • Carreira P.E.
        • Ballestin C.
        • Gomez-Reino J.J.
        Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis.
        J Pathol. 1999; 188: 63-68
        • Parks C.G.
        • Wilkerson J.
        • Rose K.M.
        • Faiq A.
        • Noroozi Farhadi P.
        • Long C.S.
        • et al.
        Association of ultraviolet radiation exposure with dermatomyositis in a national myositis patient registry.
        Arthritis Care Res (Hoboken). 2020; 72: 1636-1644
        • Pattison D.I.
        • Davies M.J.
        Actions of ultraviolet light on cellular structures.
        EXS. 2006; 96: 131-157
        • Pattison D.I.
        • Rahmanto A.S.
        • Davies M.J.
        Photo-oxidation of proteins.
        Photochem Photobiol Sci. 2012; 11: 38-53
        • Paz-Elizur T.
        • Sevilya Z.
        • Leitner-Dagan Y.
        • Elinger D.
        • Roisman L.C.
        • Livneh Z.
        DNA repair of oxidative DNA damage in human carcinogenesis: potential application for cancer risk assessment and prevention.
        Cancer Lett. 2008; 266: 60-72
        • Piskin G.
        • Bos J.D.
        • Teunissen M.B.
        Neutrophils infiltrating ultraviolet B-irradiated normal human skin display high IL-10 expression.
        Arch Dermatol Res. 2005; 296: 339-342
        • Prantner D.
        • Darville T.
        • Nagarajan U.M.
        Stimulator of IFN gene is critical for induction of IFN-beta during Chlamydia muridarum infection.
        J Immunol. 2010; 184: 2551-2560
        • Psarras A.
        • Alase A.
        • Antanaviciute A.
        • Carr I.M.
        • Md Yusof M.Y.
        • Wittmann M.
        • et al.
        Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity.
        Nat Commun. 2020; 11: 6149
        • Rana S.
        • Byrne S.N.
        • MacDonald L.J.
        • Chan C.Y.
        • Halliday G.M.
        Ultraviolet B suppresses immunity by inhibiting effector and memory T cells.
        Am J Pathol. 2008; 172: 993-1004
        • Reefman E.
        • Kuiper H.
        • Limburg P.C.
        • Kallenberg C.G.
        • Bijl M.
        Type I interferons are involved in the development of ultraviolet B-induced inflammatory skin lesions in systemic lupus erythaematosus patients.
        Ann Rheum Dis. 2008; 67: 11-18
        • Ren Y.
        • Tang J.
        • Mok M.Y.
        • Chan A.W.
        • Wu A.
        • Lau C.S.
        Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus.
        Arthritis Rheum. 2003; 48: 2888-2897
        • Rongvaux A.
        • Jackson R.
        • Harman C.C.
        • Li T.
        • West A.P.
        • de Zoete M.R.
        • et al.
        Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA.
        Cell. 2014; 159: 1563-1577
        • Sabour Alaoui S.
        • Dessirier V.
        • de Araujo E.
        • Alexaki V.I.
        • Pelekanou V.
        • Lkhider M.
        • et al.
        TWEAK affects keratinocyte G2/M growth arrest and induces apoptosis through the translocation of the AIF protein to the nucleus.
        PLoS One. 2012; 7: e33609
        • Sanders C.J.
        • Van Weelden H.
        • Kazzaz G.A.
        • Sigurdsson V.
        • Toonstra J.
        • Bruijnzeel-Koomen C.A.
        Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 100 patients using a prolonged phototest protocol.
        Br J Dermatol. 2003; 149: 131-137
        • Sarkar M.K.
        • Hile G.A.
        • Tsoi L.C.
        • Xing X.
        • Liu J.
        • Liang Y.
        • et al.
        Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa.
        Ann Rheum Dis. 2018; 77: 1653-1664
        • Sauer I.
        • Schaljo B.
        • Vogl C.
        • Gattermeier I.
        • Kolbe T.
        • Müller M.
        • et al.
        Interferons limit inflammatory responses by induction of tristetraprolin.
        Blood. 2006; 107: 4790-4797
        • Schornagel I.J.
        • Sigurdsson V.
        • Nijhuis E.H.
        • Bruijnzeel-Koomen C.A.
        • Knol E.F.
        Decreased neutrophil skin infiltration after UVB exposure in patients with polymorphous light eruption.
        J Invest Dermatol. 2004; 123: 202-206
        • Shi Z.R.
        • Cao C.X.
        • Tan G.Z.
        • Wang L.
        The association of serum anti-ribosomal P antibody with clinical and serological disorders in systemic lupus erythematosus: a systematic review and meta-analysis.
        Lupus. 2015; 24: 588-596
        • Shin M.S.
        • Kang Y.
        • Lee N.
        • Kim S.H.
        • Kang K.S.
        • Lazova R.
        • et al.
        U1-small nuclear ribonucleoprotein activates the NLRP3 inflammasome in human monocytes.
        J Immunol. 2012; 188: 4769-4775
        • Shin M.S.
        • Kang Y.
        • Lee N.
        • Wahl E.R.
        • Kim S.H.
        • Kang K.S.
        • et al.
        Self double-stranded (ds)DNA induces IL-1β production from human monocytes by activating NLRP3 inflammasome in the presence of anti-dsDNA antibodies.
        J Immunol. 2013; 190: 1407-1415
        • Shipman W.D.
        • Chyou S.
        • Ramanathan A.
        • Izmirly P.M.
        • Sharma S.
        • Pannellini T.
        • et al.
        A protective Langerhans cell-keratinocyte axis that is dysfunctional in photosensitivity.
        Sci Transl Med. 2018; 10eaap9527
        • Shreedhar V.K.
        • Pride M.W.
        • Sun Y.
        • Kripke M.L.
        • Strickland F.M.
        Origin and characteristics of ultraviolet-B radiation-induced suppressor T lymphocytes.
        J Immunol. 1998; 161: 1327-1335
        • Skopelja-Gardner S.
        • An J.
        • Tai J.
        • Tanaka L.
        • Sun X.
        • Hermanson P.
        • et al.
        The early local and systemic type I interferon responses to ultraviolet B light exposure are cGAS dependent.
        Sci Rep. 2020; 10: 7908
        • Skopelja-Gardner S.
        • Tai J.
        • Sun X.
        • Tanaka L.
        • Kuchenbecker J.A.
        • Snyder J.M.
        • et al.
        Acute skin exposure to ultraviolet light triggers neutrophil-mediated kidney inflammation.
        Proc Natl Acad Sci USA. 2021; 118e2019097118
        • Solé C.
        • Gimenez-Barcons M.
        • Ferrer B.
        • Ordi-Ros J.
        • Cortés-Hernández J.
        Microarray study reveals a transforming growth factor-β-dependent mechanism of fibrosis in discoid lupus erythematosus.
        Br J Dermatol. 2016; 175: 302-313
        • Sontheimer C.
        • Liggitt D.
        • Elkon K.B.
        Ultraviolet B irradiation causes stimulator of interferon genes-dependent production of protective type I interferon in mouse skin by recruited inflammatory monocytes.
        Arthritis Rheumatol. 2017; 69: 826-836
        • Stannard J.N.
        • Reed T.J.
        • Myers E.
        • Lowe L.
        • Sarkar M.K.
        • Xing X.
        • et al.
        Lupus skin is primed for IL-6 inflammatory responses through a keratinocyte-mediated autocrine type I interferon loop.
        J Invest Dermatol. 2017; 137: 115-122
        • Sturfelt G.
        • Truedsson L.
        • Johansen P.
        • Jonsson H.
        • Nived O.
        • Sjöholm A.G.
        Homozygous C4A deficiency in systemic lupus erythematosus: analysis of patients from a defined population.
        Clin Genet. 1990; 38: 427-433
        • Takai E.
        • Tsukimoto M.
        • Harada H.
        • Kojima S.
        Involvement of P2Y6 receptor in p38 MAPK-mediated COX-2 expression in response to UVB irradiation of human keratinocytes.
        Radiat Res. 2011; 175: 358-366
        • Takashima A.
        • Bergstresser P.R.
        Impact of UVB radiation on the epidermal cytokine network.
        Photochem Photobiol. 1996; 63: 397-400
        • Takeuchi H.
        • Gomi T.
        • Shishido M.
        • Watanabe H.
        • Suenobu N.
        Neutrophil elastase contributes to extracellular matrix damage induced by chronic low-dose UV irradiation in a hairless mouse photoaging model.
        J Dermatol Sci. 2010; 60: 151-158
        • Tsoi L.C.
        • Gharaee-Kermani M.
        • Berthier C.C.
        • Nault T.
        • Hile G.A.
        • Estadt S.N.
        • et al.
        IL18-containing 5-gene signature distinguishes histologically identical dermatomyositis and lupus erythematosus skin lesions.
        JCI Insight. 2020; 5: e139558
        • Tsoi L.C.
        • Hile G.A.
        • Berthier C.C.
        • Sarkar M.K.
        • Reed T.J.
        • Liu J.
        • et al.
        Hypersensitive IFN responses in lupus keratinocytes reveal key mechanistic determinants in cutaneous lupus.
        J Immunol. 2019; 202: 2121-2130
        • Tsukazaki N.
        • Watanabe M.
        • Shimizu K.
        • Hamasaki Y.
        • Katayama I.
        Photoprovocation test and immunohistochemical analysis of inducible nitric oxide synthase expression in patients with Sjögren's syndrome associated with photosensitivity.
        Br J Dermatol. 2002; 147: 1102-1108
        • Tumurkhuu G.
        • Chen S.
        • Montano E.N.
        • Ercan Laguna D.
        • De Los Santos G.
        • Yu J.M.
        • et al.
        Oxidative DNA damage accelerates skin inflammation in pristane-induced lupus model.
        Front Immunol. 2020; 11: 554725
        • Turnier J.L.
        • Pachman L.M.
        • Lowe L.
        • Tsoi L.C.
        • Elhaj S.
        • Menon R.
        • et al.
        Comparison of lesional juvenile myositis and lupus skin reveals overlapping yet unique disease pathophysiology.
        Arthritis Rheumatol. 2020; 73: 1062-1072
        • Van Nguyen H.
        • Di Girolamo N.
        • Jackson N.
        • Hampartzoumian T.
        • Bullpitt P.
        • Tedla N.
        • et al.
        Ultraviolet radiation-induced cytokines promote mast cell accumulation and matrix metalloproteinase production: potential role in cutaneous lupus erythematosus.
        Scand J Rheumatol. 2011; 40: 197-204
        • Vermi W.
        • Riboldi E.
        • Wittamer V.
        • Gentili F.
        • Luini W.
        • Marrelli S.
        • et al.
        Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin.
        J Exp Med. 2005; 201: 509-515
        • Villanueva E.
        • Yalavarthi S.
        • Berthier C.C.
        • Hodgin J.B.
        • Khandpur R.
        • Lin A.M.
        • et al.
        Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.
        J Immunol. 2011; 187: 538-552
        • Wang B.
        • Dong X.
        • Yuan Z.
        • Zuo Y.
        • Wang J.
        SSA/Ro antigen expressed on membrane of UVB-induced apoptotic keratinocytes is pathogenic but not detectable in supernatant of cell culture.
        Chin Med J (Engl). 1999; 112: 512-515
        • Watson R.O.
        • Bell S.L.
        • MacDuff D.A.
        • Kimmey J.M.
        • Diner E.J.
        • Olivas J.
        • et al.
        The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce type I interferons and activate autophagy.
        Cell Host Microbe. 2015; 17: 811-819
        • White M.J.
        • McArthur K.
        • Metcalf D.
        • Lane R.M.
        • Cambier J.C.
        • Herold M.J.
        • et al.
        Apoptotic caspases suppress mtDNA-induced STING-mediated type I IFN production.
        Cell. 2014; 159: 1549-1562
        • Wolf S.J.
        • Estadt S.N.
        • Theros J.
        • Moore T.
        • Ellis J.
        • Liu J.
        • et al.
        Ultraviolet light induces increased T cell activation in lupus-prone mice via type I IFN-dependent inhibition of T regulatory cells.
        J Autoimmun. 2019; 103: 102291
        • Wong D.
        • Kea B.
        • Pesich R.
        • Higgs B.W.
        • Zhu W.
        • Brown P.
        • et al.
        Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases.
        PLoS One. 2012; 7: e29161
        • Wouters C.H.
        • Diegenant C.
        • Ceuppens J.L.
        • Degreef H.
        • Stevens E.A.
        The circulating lymphocyte profiles in patients with discoid lupus erythematosus and systemic lupus erythematosus suggest a pathogenetic relationship.
        Br J Dermatol. 2004; 150: 693-700
        • Xie Y.
        • Jinnin M.
        • Zhang X.
        • Wakasugi S.
        • Makino T.
        • Inoue Y.
        • et al.
        Immunohistochemical characterization of the cellular infiltrate in discoid lupus erythematosus.
        Biosci Trends. 2011; 5: 83-88
        • Yarosh D.
        • Both D.
        • Kibitel J.
        • Anderson C.
        • Elmets C.
        • Brash D.
        • et al.
        Regulation of TNFalpha production and release in human and mouse keratinocytes and mouse skin after UV-B irradiation.
        Photodermatol Photoimmunol Photomed. 2000; 16: 263-270
        • Yin Q.
        • Xu X.
        • Lin Y.
        • Lv J.
        • Zhao L.
        • He R.
        Ultraviolet B irradiation induces skin accumulation of plasmacytoid dendritic cells: a possible role for chemerin.
        Autoimmunity. 2014; 47: 185-192
        • Zahn S.
        • Graef M.
        • Patsinakidis N.
        • Landmann A.
        • Surber C.
        • Wenzel J.
        • et al.
        Ultraviolet light protection by a sunscreen prevents interferon-driven skin inflammation in cutaneous lupus erythematosus.
        Exp Dermatol. 2014; 23: 516-518