IL-25 enhances T17 cell-mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells.

BACKGROUND

In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce T2 cytokine production by various cell types, including T2 cells, T9 cells, invariant natural killer T cells, and group 2 innate lymphoid cells, involved in T2-type immune responses. Because both T2-type and T17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 can contribute to this by enhancing T2-type immune responses. However, the precise role of IL-25 in the pathogenesis of fluorescein isothiocyanate-induced CHS is poorly understood.

OBJECTIVE

We investigated the contribution of IL-25 to CHS using Il25 mice.

METHODS

CHS was evaluated by means of measurement of ear skin thickness in mice after fluorescein isothiocyanate painting. Skin dendritic cell (DC) migration, hapten-specific T cell differentiation, and detection of IL-1β-producing cells were determined by using flow cytometry, ELISA, and immunohistochemistry, respectively.

RESULTS

In contrast to thymic stromal lymphopoietin, we found that IL-25 was not essential for skin DC migration or hapten-specific T cell differentiation in the sensitization phase of CHS. Unexpectedly, mast cell- and non-immune cell-derived IL-25 was important for hapten-specific T17 cell-mediated rather than T2 cell-mediated inflammation in the elicitation phase of CHS by enhancing T17-related, but not T2-related, cytokines in the skin. In particular, IL-1β produced by dermal DCs in response to IL-25 was crucial for hapten-specific T17 cell activation, contributing to induction of local inflammation in the elicitation phase of CHS.

CONCLUSION

Our results identify a novel IL-25 inflammatory pathway involved in induction of T17 cell-mediated, but not T2 cell-mediated, CHS. IL-25 neutralization can be a potential approach for treatment of CHS.