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Soluble DC-HIL/Gpnmb Modulates T-Lymphocyte Extravasation to Inflamed Skin

  • Author Footnotes
    4 These authors contributed equally to the work.
    Vijay Ramani
    Footnotes
    4 These authors contributed equally to the work.
    Affiliations
    Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Division of Hematology and Oncology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
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  • Author Footnotes
    4 These authors contributed equally to the work.
    Jin-Sung Chung
    Footnotes
    4 These authors contributed equally to the work.
    Affiliations
    Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
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  • Author Footnotes
    5 These authors contributed equally to the work.
    Kiyoshi Ariizumi
    Correspondence
    Correspondence: Kiyoshi Ariizumi, Department of Dermatology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas Texas 75390, USA.
    Footnotes
    5 These authors contributed equally to the work.
    Affiliations
    Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
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  • Author Footnotes
    5 These authors contributed equally to the work.
    Ponciano D. Cruz Jr.
    Footnotes
    5 These authors contributed equally to the work.
    Affiliations
    Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Dermatology Section (Medical Service), North Texas Veterans Affairs Medical Center, Dallas, Texas, USA
    Search for articles by this author
  • Author Footnotes
    4 These authors contributed equally to the work.
    5 These authors contributed equally to the work.
Published:October 22, 2021DOI:https://doi.org/10.1016/j.jid.2021.10.004
      Previously, we discovered antigen-presenting cells to express DC-HIL receptor and to secrete its soluble form (soluble DC-HIL [sDC-HIL]), both of which bind to syndecan-4 on T cells and endothelial cells (ECs), with the former binding attenuating T-cell function and the latter binding promoting angiogenesis. In this study, we examined the effects of sDC-HIL binding to EC on T-cell extravasation using an allergic contact dermatitis model in mice. The hapten oxazolone applied to ear skin in sensitized mice upregulated cutaneous expression of sDC-HIL, which downregulated the allergic reaction by reducing transendothelial migration of T cells but not other immune cells (neutrophils and mast cells). Moreover, intravenously infused sDC-HIL bound to EC in blood vessels of oxazolone-challenged skin in a scattered and patchy pattern, and intravital microscopic analysis revealed that blood-circulating T cells firmly adhere to DC-HIL–treated endothelia. This regulatory property of sDC-HIL requires syndecan-4 expression by both EC and T cells. Our findings indicate that the DC-HIL/syndecan-4 pathway mediates a cross-talk between T cells and ECs, regulating the cutaneous immune response by preventing extravasation of activated T cells into inflamed skin.

      Abbreviations:

      Ag (antigen), CHS (contact hypersensitivity), DLN (draining lymph node), EC (endothelial cell), i.v. (intravenously), KO (knockout), Ox (2-phenyl-4-ethoxymethylene-5-oxazolone), SD4 (syndecan-4), sDC-HIL (soluble DC-HIL), SVEC (simian virus 40–transformed mouse endothelial cell line), WT (wild-type)
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      References

        • Abdelmagid S.M.
        • Barbe M.F.
        • Rico M.C.
        • Salihoglu S.
        • Arango-Hisijara I.
        • Selim A.H.
        • et al.
        Osteoactivin, an anabolic factor that regulates osteoblast differentiation and function.
        Exp Cell Res. 2008; 314: 2334-2351
        • Abtin A.
        • Jain R.
        • Mitchell A.J.
        • Roediger B.
        • Brzoska A.J.
        • Tikoo S.
        • et al.
        Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection.
        Nat Immunol. 2014; 15: 45-53
        • Akiyoshi H.
        • Chung J.S.
        • Tomihari M.
        • Cruz Jr., P.D.
        • Ariizumi K.
        Depleting syndecan-4+ T lymphocytes using toxin-bearing dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand: a new opportunity for treating activated T cell-driven disease.
        J Immunol. 2010; 184: 3554-3561
        • Beerling E.
        • Ritsma L.
        • Vrisekoop N.
        • Derksen P.W.
        • van Rheenen J.
        Intravital microscopy: new insights into metastasis of tumors.
        J Cell Sci. 2011; 124: 299-310
        • Byrne S.N.
        • Limón-Flores A.Y.
        • Ullrich S.E.
        Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression.
        J Immunol. 2008; 180: 4648-4655
        • Cao L.Y.
        • Chung J.S.
        • Teshima T.
        • Feigenbaum L.
        • Cruz Jr., P.D.
        • Jacobe H.T.
        • et al.
        Myeloid-derived suppressor cells in psoriasis are an expanded population exhibiting diverse T-cell-suppressor mechanisms.
        J Invest Dermatol. 2016; 136: 1801-1810
        • Chavakis E.
        • Choi E.Y.
        • Chavakis T.
        Novel aspects in the regulation of the leukocyte adhesion cascade.
        Thromb Haemost. 2009; 102: 191-197
        • Chung J.S.
        • Cruz Jr., P.D.
        • Ariizumi K.
        Inhibition of T-cell activation by syndecan-4 is mediated by CD148 through protein tyrosine phosphatase activity.
        Eur J Immunol. 2011; 41: 1794-1799
        • Chung J.S.
        • Dougherty I.
        • Cruz Jr., P.D.
        • Ariizumi K.
        Syndecan-4 mediates the coinhibitory function of DC-HIL on T cell activation.
        J Immunol. 2007; 179: 5778-5784
        • Chung J.S.
        • Sato K.
        • Dougherty I.I.
        • Cruz Jr., P.D.
        • Ariizumi K.
        DC-HIL is a negative regulator of T lymphocyte activation.
        Blood. 2007; 109: 4320-4327
        • Chung J.S.
        • Tamura K.
        • Akiyoshi H.
        • Cruz Jr., P.D.
        • Ariizumi K.
        The DC-HIL/syndecan-4 pathway regulates autoimmune responses through myeloid-derived suppressor cells.
        J Immunol. 2014; 192: 2576-2584
        • Chung J.S.
        • Tamura K.
        • Cruz Jr., P.D.
        • Ariizumi K.
        DC-HIL-expressing myelomonocytic cells are critical promoters of melanoma growth.
        J Invest Dermatol. 2014; 134: 2784-2794
        • Chung J.S.
        • Tomihari M.
        • Tamura K.
        • Kojima T.
        • Cruz Jr., P.D.
        • Ariizumi K.
        The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity responsible for graft-versus-host disease.
        Immunology. 2013; 138: 173-182
        • Deban L.
        • Russo R.C.
        • Sironi M.
        • Moalli F.
        • Scanziani M.
        • Zambelli V.
        • et al.
        Regulation of leukocyte recruitment by the long pentraxin PTX3.
        Nat Immunol. 2010; 11: 328-334
        • Engeman T.
        • Gorbachev A.V.
        • Kish D.D.
        • Fairchild R.L.
        The intensity of neutrophil infiltration controls the number of antigen-primed CD8 T cells recruited into cutaneous antigen challenge sites.
        J Leukoc Biol. 2004; 76: 941-949
        • Fiorentini C.
        • Bodei S.
        • Bedussi F.
        • Fragni M.
        • Bonini S.A.
        • Simeone C.
        • et al.
        GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity.
        Exp Cell Res. 2014; 323: 100-111
        • Frangogiannis N.G.
        Regulation of the inflammatory response in cardiac repair.
        Circ Res. 2012; 110: 159-173
        • Goebeler M.
        • Trautmann A.
        • Voss A.
        • Bröcker E.V.
        • Toksoy A.
        • Gillitzer R.
        Differential and sequential expression of multiple chemokines during elicitation of allergic contact hypersensitivity.
        Am J Pathol. 2001; 158: 431-440
        • Grabbe S.
        • Schwarz T.
        Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity.
        Immunol Today. 1998; 19: 37-44
        • Hajishengallis G.
        • Chavakis T.
        Endogenous modulators of inflammatory cell recruitment.
        Trends Immunol. 2013; 34: 1-6
        • Hart P.H.
        • Grimbaldeston M.A.
        • Swift G.J.
        • Jaksic A.
        • Noonan F.P.
        • Finlay-Jones J.J.
        Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice.
        J Exp Med. 1998; 187: 2045-2053
        • Hidai C.
        • Kawana M.
        • Kitano H.
        • Kokubun S.
        Discoidin domain of Del1 protein contributes to its deposition in the extracellular matrix.
        Cell Tissue Res. 2007; 330: 83-95
        • Honda T.
        • Egawa G.
        • Grabbe S.
        • Kabashima K.
        Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis.
        J Invest Dermatol. 2013; 133: 303-315
        • Julien S.
        • Grimshaw M.J.
        • Sutton-Smith M.
        • Coleman J.
        • Morris H.R.
        • Dell A.
        • et al.
        Sialyl-Lewis(x) on P-selectin glycoprotein ligand-1 is regulated during differentiation and maturation of dendritic cells: a mechanism involving the glycosyltransferases C2GnT1 and ST3Gal I.
        J Immunol. 2007; 179: 5701-5710
        • Kempf T.
        • Zarbock A.
        • Widera C.
        • Butz S.
        • Stadtmann A.
        • Rossaint J.
        • et al.
        GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice.
        Nat Med. 2011; 17: 581-588
        • Kobayashi M.
        • Chung J.S.
        • Beg M.
        • Arriaga Y.
        • Verma U.
        • Courtney K.
        • et al.
        Blocking monocytic myeloid-derived suppressor cell function via anti-DC-HIL/GPNMB antibody restores the in vitro integrity of T cells from cancer patients.
        Clin Cancer Res. 2019; 25: 828-838
        • Lazennec G.
        • Richmond A.
        Chemokines and chemokine receptors: new insights into cancer-related inflammation.
        Trends Mol Med. 2010; 16: 133-144
        • Lee P.Y.
        • Wang J.X.
        • Parisini E.
        • Dascher C.C.
        • Nigrovic P.A.
        Ly6 family proteins in neutrophil biology.
        J Leukoc Biol. 2013; 94: 585-594
        • Muller W.A.
        Getting leukocytes to the site of inflammation.
        Vet Pathol. 2013; 50: 7-22
        • Newton P.
        • O'Boyle G.
        • Jenkins Y.
        • Ali S.
        • Kirby J.A.
        T cell extravasation: demonstration of synergy between activation of CXCR3 and the T cell receptor.
        Mol Immunol. 2009; 47: 485-492
        • Nolz J.C.
        Molecular mechanisms of CD8(+) T cell trafficking and localization.
        Cell Mol Life Sci. 2015; 72: 2461-2473
        • Ramani V.
        • Teshima T.
        • Tamura K.
        • Chung J.S.
        • Kobayashi M.
        • Cruz Jr., P.D.
        • et al.
        Melanoma-derived soluble DC-HIL/GPNMB promotes metastasis by excluding T-lymphocytes from the pre-metastatic niches.
        J Invest Dermatol. 2018; 138: 2443-2451
        • Safadi F.F.
        • Xu J.
        • Smock S.L.
        • Rico M.C.
        • Owen T.A.
        • Popoff S.N.
        Cloning and characterization of osteoactivin, a novel cDNA expressed in osteoblasts.
        J Cell Biochem. 2001; 84: 12-26
        • Schnoor M.
        • Alcaide P.
        • Voisin M.B.
        • van Buul J.D.
        Crossing the vascular wall: common and unique mechanisms exploited by different leukocyte subsets during extravasation.
        Mediators Inflamm. 2015; 2015: 946509
        • Spring K.
        • Chabot C.
        • Langlois S.
        • Lapointe L.
        • Trinh N.T.
        • Caron C.
        • et al.
        Tyrosine phosphorylation of DEP-1/CD148 as a mechanism controlling Src kinase activation, endothelial cell permeability, invasion, and capillary formation.
        Blood. 2012; 120: 2745-2756
        • Stockton B.M.
        • Cheng G.
        • Manjunath N.
        • Ardman B.
        • von Andrian U.H.
        Negative regulation of T cell homing by CD43.
        Immunity. 1998; 8: 373-381
        • Tanaka T.
        • McRae B.J.
        • Cho K.
        • Cook R.
        • Fraki J.E.
        • Johnson D.A.
        • et al.
        Mammalian tissue trypsin-like enzymes. Comparative reactivities of human skin tryptase, human lung tryptase, and bovine trypsin with peptide 4-nitroanilide and thioester substrates.
        J Biol Chem. 1983; 258: 13552-13557
        • Taya M.
        • Hammes S.R.
        Glycoprotein non-metastatic melanoma protein B (GPNMB) and cancer: a novel potential therapeutic target.
        Steroids. 2018; 133: 102-107

      Supplementary References

        • Chung J.S.
        • Sato K.
        • Dougherty I.I.
        • Cruz Jr., P.D.
        • Ariizumi K.
        DC-HIL is a negative regulator of T lymphocyte activation.
        Blood. 2007; 109: 4320-4327
        • Chung J.S.
        • Yudate T.
        • Tomihari M.
        • Akiyoshi H.
        • Cruz Jr., P.D.
        • Ariizumi K.
        Binding of DC-HIL to dermatophytic fungi induces tyrosine phosphorylation and potentiates antigen presenting cell function.
        J Immunol. 2009; 183: 5190-5198
        • Li W.
        • Mukouyama Y.S.
        Whole-mount immunohistochemical analysis for embryonic limb skin vasculature: a model system to study vascular branching morphogenesis in embryo.
        J Vis Exp. 2011; 51: 2620