| First Author | Gatzka M | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 11 | Pages | 5477-88 |
| PubMed ID | 24190659 | Mgi Jnum | J:207148 |
| Mgi Id | MGI:5554513 | Doi | 10.4049/jimmunol.1300976 |
| Citation | Gatzka M, et al. (2013) Reduction of CD18 promotes expansion of inflammatory gammadelta T cells collaborating with CD4+ T cells in chronic murine psoriasiform dermatitis. J Immunol 191(11):5477-88 |
| abstractText | IL-17 is a critical factor in the pathogenesis of psoriasis and other inflammatory diseases. The impact of gammadelta T cells, accounting for an important source of IL-17 in acute murine IL-23- and imiquimod-induced skin inflammation, in human psoriasis is still unclear. Using the polygenic CD18(hypo) PL/J psoriasis mouse model spontaneously developing chronic psoriasiform dermatitis due to reduced CD18/beta2 integrin expression to 2-16% of wild-type levels, we investigated in this study the influence of adhesion molecule expression on generation of inflammatory gammadelta T cells and analyzed the occurrence of IL-17-producing gammadelta and CD4(+) T cells at different disease stages. Severity of CD18(hypo) PL/J psoriasiform dermatitis correlated with a loss of skin-resident Vgamma5(+) T cells and concurrent skin infiltration with IL-17(+), IL-22(+), and TNF-alpha(+) gammadeltaTCR(low) cells preceded by increases in Vgamma4(+) T cells in local lymph nodes. In vitro, reduced CD18 levels promoted expansion of inflammatory memory-type gammadelta T cells in response to IL-7. Similar to IL-17 or IL-23/p19 depletion, injection of diseased CD18(hypo) PL/J mice with anti-gammadeltaTCR Abs significantly reduced skin inflammation and largely eliminated pathological gammadelta and CD4(+) T cells. Moreover, CD18(hypo) gammadelta T cells induced allogeneic CD4(+) T cell responses more potently than CD18(wt) counterparts and, upon adoptive transfer, triggered psoriasiform dermatitis in susceptible hosts. These results demonstrate a novel function of reduced CD18 levels in generation of pathological gammadelta T cells that was confirmed by detection of increases in CD18(low) gammadelta T cells in psoriasis patients and may also have implications for other inflammatory diseases. |
