Advertisement
Journal of Investigative Dermatology Home

Inhibition of CtBP-Regulated Proinflammatory Gene Transcription Attenuates Psoriatic Skin Inflammation

  • Author Footnotes
    9 These authors contributed equally to this work.
    Hong Li
    Footnotes
    9 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
    Search for articles by this author
  • Author Footnotes
    9 These authors contributed equally to this work.
    Caiguo Zhang
    Footnotes
    9 These authors contributed equally to this work.
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
    Search for articles by this author
  • Li Bian
    Affiliations
    Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
    Search for articles by this author
  • Hui Deng
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Department of Dermatology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
    Search for articles by this author
  • Melanie Blevins
    Affiliations
    Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
    Search for articles by this author
  • Gangwen Han
    Affiliations
    Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Department of Dermatology, Peking University International Hospital, Beijing, China
    Search for articles by this author
  • Bin Fan
    Affiliations
    Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
    Search for articles by this author
  • Chunxia Yang
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
    Search for articles by this author
  • Rui Zhao
    Affiliations
    Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
    Search for articles by this author
  • Whitney High
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
    Search for articles by this author
  • David Norris
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Veterans Affairs Medical Center, VA Eastern Colorado Health Care System, Aurora, Colorado, USA
    Search for articles by this author
  • Mayumi Fujita
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Veterans Affairs Medical Center, VA Eastern Colorado Health Care System, Aurora, Colorado, USA
    Search for articles by this author
  • Xiao-Jing Wang
    Affiliations
    Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

    Veterans Affairs Medical Center, VA Eastern Colorado Health Care System, Aurora, Colorado, USA
    Search for articles by this author
  • Mingxia Huang
    Correspondence
    Correspondence: Mingxia Huang, Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, 12801 East 17th Avenue, Mail Stop 8127, Aurora, Colorado 80045, USA.
    Affiliations
    Department of Dermatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
    Search for articles by this author
  • Author Footnotes
    9 These authors contributed equally to this work.
      Psoriasis is a chronic immune-mediated disease characterized by excessive proliferation of epidermal keratinocytes and increased immune cell infiltration to the skin. Although it is well-known that psoriasis pathogenesis is driven by aberrant production of proinflammatory cytokines, the mechanisms underlying the imbalance between proinflammatory and anti-inflammatory cytokine expression are incompletely understood. In this study, we report that the transcriptional coregulators CtBP1 and 2 can transactivate a common set of proinflammatory genes both in the skin of imiquimod-induced mouse psoriasis model and in human keratinocytes and macrophages stimulated by imiquimod. We find that mice overexpressing CtBP1 in epidermal keratinocytes display severe skin inflammation phenotypes with increased expression of T helper type 1 and T helper type 17 cytokines. We also find that the expression of CtBPs and CtBP-target genes is elevated both in human psoriatic lesions and in the mouse imiquimod psoriasis model. Moreover, we were able to show that topical treatment with a peptidic inhibitor of CtBP effectively suppresses the CtBP-regulated proinflammatory gene expression and thus attenuates psoriatic inflammation in the imiquimod mouse model. Together, our findings suggest to our knowledge previously unreported strategies for therapeutic modulation of the immune response in inflammatory skin diseases.

      Graphical abstract

      Abbreviations:

      AP-1 (activator protein-1), ChIP (chromatin immunoprecipitation), IHC (immunohistochemistry), IMQ (imiquimod), KC (keratinocyte), PP (psoriatic lesion)
      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

        • Alexander H.
        • Nestle F.O.
        Pathogenesis and immunotherapy in cutaneous psoriasis: what can rheumatologists learn?.
        Curr Opin Rheumatol. 2017; 29: 71-78
        • Balasubramanian P.
        • Zhao L.J.
        • Chinnadurai G.
        Nicotinamide adenine dinucleotide stimulates oligomerization, interaction with adenovirus E1A and an intrinsic dehydrogenase activity of CtBP.
        FEBS Lett. 2003; 537: 157-160
        • Baliwag J.
        • Barnes D.H.
        • Johnston A.
        Cytokines in psoriasis.
        Cytokine. 2015; 73: 342-350
        • Bellesis A.G.
        • Jecrois A.M.
        • Hayes J.A.
        • Schiffer C.A.
        • Royer Jr., W.E.
        Assembly of human C-terminal binding protein (CtBP) into tetramers.
        J Biol Chem. 2018; 293: 9101-9112
        • Blevins M.A.
        • Zhang C.
        • Zhang L.
        • Li H.
        • Li X.
        • Norris D.A.
        • et al.
        CPP-E1A fusion peptides inhibit CtBP-mediated transcriptional repression.
        Mol Oncol. 2018; 12: 1358-1373
        • Bouchaud G.
        • Gehrke S.
        • Krieg C.
        • Kolios A.
        • Hafner J.
        • Navarini A.A.
        • et al.
        Epidermal IL-15Rα acts as an endogenous antagonist of psoriasiform inflammation in mouse and man.
        J Exp Med. 2013; 210: 2105-2117
        • Boxer L.D.
        • Barajas B.
        • Tao S.
        • Zhang J.
        • Khavari P.A.
        ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes.
        Genes Dev. 2014; 28: 2013-2026
        • Chen Z.
        • Dong W.H.
        • Qiu Z.M.
        • Li Q.G.
        The monocyte-derived exosomal CLMAT3 activates the CtBP2-p300-NF-κB transcriptional complex to induce proinflammatory cytokines in ALI.
        Mol Ther Nucleic Acids. 2020; 21: 1100-1110
        • Chinnadurai G.
        The transcriptional corepressor CtBP: a foe of multiple tumor suppressors.
        Cancer Res. 2009; 69: 731-734
        • Chiricozzi A.
        • Guttman-Yassky E.
        • Suárez-Fariñas M.
        • Nograles K.E.
        • Tian S.
        • Cardinale I.
        • et al.
        Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis.
        J Invest Dermatol. 2011; 131: 677-687
        • Choi H.J.
        • Lee J.M.
        • Kim H.
        • Nam H.J.
        • Shin H.J.
        • Kim D.
        • et al.
        Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer.
        Biochem Biophys Res Commun. 2010; 400: 396-402
        • Dcona M.M.
        • Morris B.L.
        • Ellis K.C.
        • Grossman S.R.
        CtBP- an emerging oncogene and novel small molecule drug target: advances in the understanding of its oncogenic action and identification of therapeutic inhibitors.
        Cancer Biol Ther. 2017; 18: 379-391
        • Deng H.
        • Li F.
        • Li H.
        • Deng Y.
        • Liu J.
        • Wang D.
        • et al.
        CtBP1 overexpression in keratinocytes perturbs skin homeostasis.
        J Invest Dermatol. 2014; 134: 1323-1331
        • Di Cesare A.
        • Di Meglio P.
        • Nestle F.O.
        The IL-23/Th17 axis in the immunopathogenesis of psoriasis.
        J Invest Dermatol. 2009; 129: 1339-1350
        • Di L.J.
        • Byun J.S.
        • Wong M.M.
        • Wakano C.
        • Taylor T.
        • Bilke S.
        • et al.
        Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer.
        Nat Commun. 2013; 4: 1449
        • El Malki K.
        • Karbach S.H.
        • Huppert J.
        • Zayoud M.
        • Reissig S.
        • Schüler R.
        • et al.
        An alternative pathway of imiquimod-induced psoriasis-like skin inflammation in the absence of interleukin-17 receptor a signaling.
        J Invest Dermatol. 2013; 133: 441-451
        • Flutter B.
        • Nestle F.O.
        TLRs to cytokines: mechanistic insights from the imiquimod mouse model of psoriasis.
        Eur J Immunol. 2013; 43: 3138-3146
        • Griffith A.D.
        • Zaidi A.K.
        • Pietro A.
        • Hadiono M.
        • Yang J.S.
        • Davis R.
        • et al.
        A requirement for slc15a4 in imiquimod-induced systemic inflammation and psoriasiform inflammation in mice.
        Sci Rep. 2018; 8: 14451
        • Grossman R.M.
        • Krueger J.
        • Yourish D.
        • Granelli-Piperno A.
        • Murphy D.P.
        • May L.T.
        • et al.
        Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes.
        Proc Natl Acad Sci USA. 1989; 86: 6367-6371
        • Ha H.L.
        • Wang H.
        • Pisitkun P.
        • Kim J.C.
        • Tassi I.
        • Tang W.
        • et al.
        IL-17 drives psoriatic inflammation via distinct, target cell-specific mechanisms.
        Proc Natl Acad Sci USA. 2014; 111: E3422-E3431
        • Han G.
        • Bian L.
        • Li F.
        • Cotrim A.
        • Wang D.
        • Lu J.
        • et al.
        Preventive and therapeutic effects of Smad7 on radiation-induced oral mucositis.
        Nat Med. 2013; 19: 421-428
        • Han G.
        • Williams C.A.
        • Salter K.
        • Garl P.J.
        • Li A.G.
        • Wang X.J.
        A role for TGFbeta signaling in the pathogenesis of psoriasis.
        J Invest Dermatol. 2010; 130: 371-377
        • Helmick C.G.
        • Lee-Han H.
        • Hirsch S.C.
        • Baird T.L.
        • Bartlett C.L.
        Prevalence of psoriasis among adults in the U.S.: 2003–2006 and 2009–2010 National Health and Nutrition Examination Surveys.
        Am J Prev Med. 2014; 47: 37-45
        • Hirahara K.
        • Ghoreschi K.
        • Laurence A.
        • Yang X.P.
        • Kanno Y.
        • O'Shea J.J.
        Signal transduction pathways and transcriptional regulation in Th17 cell differentiation.
        Cytokine Growth Factor Rev. 2010; 21: 425-434
        • Huang X.
        • Chen J.
        • Zeng W.
        • Wu X.
        • Chen M.
        • Chen X.
        Membrane-enriched solute carrier family 2 member 1 (SLC2A1/GLUT1) in psoriatic keratinocytes confers sensitivity to 2-deoxy-D-glucose (2-DG) treatment.
        Exp Dermatol. 2019; 28: 198-201
        • Ichikawa K.
        • Kubota Y.
        • Nakamura T.
        • Weng J.S.
        • Tomida T.
        • Saito H.
        • et al.
        MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP.
        Mol Cell. 2015; 58: 35-46
        • Jecrois A.M.
        • Dcona M.M.
        • Deng X.
        • Bandyopadhyay D.
        • Grossman S.R.
        • Schiffer C.A.
        • et al.
        Cryo-EM structure of CtBP2 confirms tetrameric architecture.
        Structure. 2021; 29: 310-319.e5
        • Jordan C.T.
        • Cao L.
        • Roberson E.D.
        • Duan S.
        • Helms C.A.
        • Nair R.P.
        • et al.
        Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis.
        Am J Hum Genet. 2012; 90: 796-808
        • Karin M.
        The regulation of AP-1 activity by mitogen-activated protein kinases.
        J Biol Chem. 1995; 270: 16483-16486
        • Kim S.J.
        • Glick A.
        • Sporn M.B.
        • Roberts A.B.
        Characterization of the promoter region of the human transforming growth factor-beta 1 gene.
        J Biol Chem. 1989; 264: 402-408
        • Kim Y.M.
        • Im J.Y.
        • Han S.H.
        • Kang H.S.
        • Choi I.
        IFN-gamma up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages.
        J Immunol. 2000; 165: 3198-3205
        • Korn T.
        • Bettelli E.
        • Oukka M.
        • Kuchroo V.K.
        IL-17 and Th17 cells.
        Annu Rev Immunol. 2009; 27: 485-517
        • Kumar V.
        • Carlson J.E.
        • Ohgi K.A.
        • Edwards T.A.
        • Rose D.W.
        • Escalante C.R.
        • et al.
        Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase.
        Mol Cell. 2002; 10: 857-869
        • Li A.G.
        • Wang D.
        • Feng X.H.
        • Wang X.J.
        Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder.
        EMBO J. 2004; 23: 1770-1781
        • Li B.
        • Tsoi L.C.
        • Swindell W.R.
        • Gudjonsson J.E.
        • Tejasvi T.
        • Johnston A.
        • et al.
        Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq provides insights into disease mechanisms.
        J Invest Dermatol. 2014; 134: 1828-1838
        • Li H.
        • Zhang C.
        • Yang C.
        • Blevins M.
        • Norris D.
        • Zhao R.
        • et al.
        C-terminal binding proteins 1 and 2 in traumatic brain injury-induced inflammation and their inhibition as an approach for anti-inflammatory treatment.
        Int J Biol Sci. 2020; 16: 1107-1120
        • Li M.
        • Riddle S.
        • Zhang H.
        • D'Alessandro A.
        • Flockton A.
        • Serkova N.J.
        • et al.
        Metabolic reprogramming regulates the proliferative and inflammatory phenotype of adventitial fibroblasts in pulmonary hypertension through the transcriptional corepressor C-terminal binding protein-1 [published correction appears in Circulation 2019;139:e1].
        Circulation. 2016; 134: 1105-1121
        • Lin X.
        • Sun B.
        • Liang M.
        • Liang Y.Y.
        • Gast A.
        • Hildebrand J.
        • et al.
        Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding.
        Mol Cell. 2003; 11: 1389-1396
        • Madison D.L.
        • Wirz J.A.
        • Siess D.
        • Lundblad J.R.
        Nicotinamide adenine dinucleotide-induced multimerization of the co-repressor CtBP1 relies on a switching tryptophan.
        J Biol Chem. 2013; 288: 27836-27848
        • Matsumoto R.
        • Dainichi T.
        • Tsuchiya S.
        • Nomura T.
        • Kitoh A.
        • Hayden M.S.
        • et al.
        Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation.
        JCI Insight. 2018; 3e121175
        • Medzhitov R.
        • Horng T.
        Transcriptional control of the inflammatory response.
        Nat Rev Immunol. 2009; 9: 692-703
        • Müller A.
        • Hennig A.
        • Lorscheid S.
        • Grondona P.
        • Schulze-Osthoff K.
        • Hailfinger S.
        • et al.
        IκBζ is a key transcriptional regulator of IL-36-driven psoriasis-related gene expression in keratinocytes.
        Proc Natl Acad Sci USA. 2018; 115: 10088-10093
        • Nerurkar L.
        • McColl A.
        • Graham G.
        • Cavanagh J.
        The systemic response to topical Aldara treatment is mediated through direct TLR7 stimulation as imiquimod enters the circulation.
        Sci Rep. 2017; 7: 16570
        • Nestle F.O.
        • Kaplan D.H.
        • Barker J.
        Psoriasis.
        N Engl J Med. 2009; 361: 496-509
        • Novick D.
        • Kim S.
        • Kaplanski G.
        • Dinarello C.A.
        Interleukin-18, more than a Th1 cytokine.
        Semin Immunol. 2013; 25: 439-448
        • Pan F.
        • Yu H.
        • Dang E.V.
        • Barbi J.
        • Pan X.
        • Grosso J.F.
        • et al.
        Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T cells.
        Science. 2009; 325: 1142-1146
        • Poligone B.
        • Hayden M.S.
        • Chen L.
        • Pentland A.P.
        • Jimi E.
        • Ghosh S.
        A role for NF-κB activity in skin hyperplasia and the development of keratoacanthomata in mice.
        PLoS One. 2013; 8: e71887
        • Ray S.K.
        • Li H.J.
        • Metzger E.
        • Schüle R.
        • Leiter A.B.
        CtBP and associated LSD1 are required for transcriptional activation by NeuroD1 in gastrointestinal endocrine cells.
        Mol Cell Biol. 2014; 34: 2308-2317
        • Saijo K.
        • Collier J.G.
        • Li A.C.
        • Katzenellenbogen J.A.
        • Glass C.K.
        An ADIOL-ERβ-CtBP transrepression pathway negatively regulates microglia-mediated inflammation.
        Cell. 2011; 145: 584-595
        • Sakurai K.
        • Dainichi T.
        • Garcet S.
        • Tsuchiya S.
        • Yamamoto Y.
        • Kitoh A.
        • et al.
        Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis.
        J Allergy Clin Immunol. 2019; 144: 1036-1049
        • Sano S.
        • Chan K.S.
        • Carbajal S.
        • Clifford J.
        • Peavey M.
        • Kiguchi K.
        • et al.
        Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model.
        Nat Med. 2005; 11: 43-49
        • Shen Y.
        • Kapfhamer D.
        • Minnella A.M.
        • Kim J.E.
        • Won S.J.
        • Chen Y.
        • et al.
        Bioenergetic state regulates innate inflammatory responses through the transcriptional co-repressor CtBP.
        Nat Commun. 2017; 8: 624
        • Shirakihara T.
        • Horiguchi K.
        • Miyazawa K.
        • Ehata S.
        • Shibata T.
        • Morita I.
        • et al.
        TGFβ regulates isoform switching of FGF receptors and epithelial-mesenchymal transition.
        EMBO J. 2011; 30: 783-795
        • Smale S.T.
        Selective transcription in response to an inflammatory stimulus.
        Cell. 2010; 140: 833-844
        • Swindell W.R.
        • Johnston A.
        • Carbajal S.
        • Han G.
        • Wohn C.
        • Lu J.
        • et al.
        Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.
        PLOS ONE. 2011; 6: e18266
        • Swindell W.R.
        • Remmer H.A.
        • Sarkar M.K.
        • Xing X.
        • Barnes D.H.
        • Wolterink L.
        • et al.
        Proteogenomic analysis of psoriasis reveals discordant and concordant changes in mRNA and protein abundance.
        Genome Med. 2015; 7: 86
        • Takeshita J.
        • Grewal S.
        • Langan S.M.
        • Mehta N.N.
        • Ogdie A.
        • Van Voorhees A.S.
        • et al.
        Psoriasis and comorbid diseases: epidemiology.
        J Am Acad Dermatol. 2017; 76: 377-390
        • Tortola L.
        • Rosenwald E.
        • Abel B.
        • Blumberg H.
        • Schäfer M.
        • Coyle A.J.
        • et al.
        Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk.
        J Clin Invest. 2012; 122: 3965-3976
        • Tsuchida K.
        • Chaki H.
        • Takakura T.
        • Yokotani J.
        • Aikawa Y.
        • Shiozawa S.
        • et al.
        Design, synthesis, and biological evaluation of new cyclic disulfide decapeptides that inhibit the binding of AP-1 to DNA.
        J Med Chem. 2004; 47: 4239-4246
        • van der Fits L.
        • Mourits S.
        • Voerman J.S.
        • Kant M.
        • Boon L.
        • Laman J.D.
        • et al.
        Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis.
        J Immunol. 2009; 182: 5836-5845
        • Verger A.
        • Quinlan K.G.
        • Crofts L.A.
        • Spanò S.
        • Corda D.
        • Kable E.P.
        • et al.
        Mechanisms directing the nuclear localization of the CtBP family proteins.
        Mol Cell Biol. 2006; 26: 4882-4894
        • Vinter H.
        • Kragballe K.
        • Steiniche T.
        • Gaestel M.
        • Iversen L.
        • Johansen C.
        Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice.
        Br J Dermatol. 2016; 174: 1011-1021
        • Vogl T.
        • Eisenblätter M.
        • Völler T.
        • Zenker S.
        • Hermann S.
        • van Lent P.
        • et al.
        Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity.
        Nat Commun. 2014; 5: 4593
        • Wang J.
        • Lee S.
        • Teh C.E.
        • Bunting K.
        • Ma L.
        • Shannon M.F.
        The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL-2 gene activation in T cells.
        Int Immunol. 2009; 21: 227-235
        • Wang X.J.
        • Liefer K.M.
        • Tsai S.
        • O'Malley B.W.
        • Roop D.R.
        Development of gene-switch transgenic mice that inducibly express transforming growth factor beta1 in the epidermis.
        Proc Natl Acad Sci USA. 1999; 96: 8483-8488
        • Weigert C.
        • Sauer U.
        • Brodbeck K.
        • Pfeiffer A.
        • Haring H.U.
        • Schleicher E.D.
        AP-1 proteins mediate hyperglycemia-induced activation of the human TGF-beta1 promoter in mesangial cells.
        J Am Soc Nephrol. 2000; 11: 2007-2016
        • Winer J.
        • Jung C.K.
        • Shackel I.
        • Williams P.M.
        Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro.
        Anal Biochem. 1999; 270: 41-49
        • Wohn C.
        • Ober-Blöbaum J.L.
        • Haak S.
        • Pantelyushin S.
        • Cheong C.
        • Zahner S.P.
        • et al.
        Langerin(neg) conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice.
        Proc Natl Acad Sci USA. 2013; 110: 10723-10728
        • Works M.G.
        • Yin F.
        • Yin C.C.
        • Yiu Y.
        • Shew K.
        • Tran T.T.
        • et al.
        Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis.
        J Immunol. 2014; 193: 3278-3287
        • Worley M.I.
        • Alexander L.A.
        • Hariharan I.K.
        CtBP impedes JNK- and Upd/STAT-driven cell fate misspecifications in regenerating Drosophila imaginal discs.
        eLife. 2018; 7: e30391
        • Zhang Q.
        • Yoshimatsu Y.
        • Hildebrand J.
        • Frisch S.M.
        • Goodman R.H.
        Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP.
        Cell. 2003; 115: 177-186
        • Zhou P.
        • Wan X.
        • Zou Y.
        • Chen Z.
        • Zhong A.
        Transforming growth factor beta (TGF-β) is activated by the CtBP2-p300-AP1 transcriptional complex in chronic renal failure.
        Int J Biol Sci. 2020; 16: 204-215