| First Author | Nielsen MM | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 7 | Pages | 2975-83 |
| PubMed ID | 24600030 | Mgi Jnum | J:210021 |
| Mgi Id | MGI:5569415 | Doi | 10.4049/jimmunol.1301689 |
| Citation | Nielsen MM, et al. (2014) IL-1beta-dependent activation of dendritic epidermal T cells in contact hypersensitivity. J Immunol 192(7):2975-83 |
| abstractText | Substances that penetrate the skin surface can act as allergens and induce a T cell-mediated inflammatory skin disease called contact hypersensitivity (CHS). IL-17 is a key cytokine in CHS and was originally thought to be produced solely by CD4(+) T cells. However, it is now known that several cell types, including gammadelta T cells, can produce IL-17. In this study, we determine the role of gammadelta T cells, especially dendritic epidermal T cells (DETCs), in CHS. Using a well-established model for CHS in which 2,4-dinitrofluorobenzene (DNFB) is used as allergen, we found that gammadelta T cells are important players in CHS. Thus, more IL-17-producing DETCs appear in the skin following exposure to DNFB in wild-type mice, and DNFB-induced ear swelling is reduced by approximately 50% in TCRdelta(-/-) mice compared with wild-type mice. In accordance, DNFB-induced ear swelling was reduced by approximately 50% in IL-17(-/-) mice. We show that DNFB triggers DETC activation and IL-1beta production in the skin and that keratinocytes produce IL-1beta when stimulated with DNFB. We find that DETCs activated in vitro by incubation with anti-CD3 and IL-1beta produce IL-17. Importantly, we demonstrate that the IL-1R antagonist anakinra significantly reduces CHS responses, as measured by decreased ear swelling, inhibition of local DETC activation, and a reduction in the number of IL-17(+) gammadelta T cells and DETCs in the draining lymph nodes. Taken together, we show that DETCs become activated and produce IL-17 in an IL-1beta-dependent manner during CHS, suggesting a key role for DETCs in CHS. |
