| First Author | Campbell JJ | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 9 | Pages | 3129-3136 |
| PubMed ID | 28972090 | Mgi Jnum | J:250710 |
| Mgi Id | MGI:6103492 | Doi | 10.4049/jimmunol.1700826 |
| Citation | Campbell JJ, et al. (2017) IL-17-Secreting gammadelta T Cells Are Completely Dependent upon CCR6 for Homing to Inflamed Skin. J Immunol 199(9):3129-3136 |
| abstractText | mAbs that neutralize IL-17 or its receptor have proven efficacious in treating moderate-to-severe psoriasis, confirming IL-17 as an important driver of this disease. In mice, a rare population of T cells, gammadeltaT17 cells, appears to be a dominant source of IL-17 in experimental psoriasis. These cells traffic between lymph nodes and the skin, and are identified by their coexpression of the TCR variable regions gamma4 and delta4. These cells are homologous to the Vgamma9Vdelta2 T cell population identified in human psoriatic plaques. In this study we report that a potent and specific small molecule antagonist of the CCR6 chemokine receptor, CCX2553, was efficacious in reducing multiple aspects of psoriasis in two different murine models of the disease. Administration of CCX2553 ameliorated skin inflammation in both the IL-23-induced ear swelling model and the topical imiquimod model, and significantly reduced the number of gammadeltaT17 cells in inflamed skin. gammadeltaT17 cells were greatly reduced in imiquimod-treated skin of CCR6(-/-) mice, but adoptively transferred wild-type (CCR6(+/+)) gammadeltaT17 cells homed normally to the skin of imiquimod-treated CCR6(-/-) mice. Our data suggest that gammadeltaT17 cells are completely dependent on CCR6 for homing to psoriasiform skin. Thus, CCR6 may constitute a novel target for a mechanistically distinct therapeutic approach to treating psoriasis. |
