IL-25 enhances Th17 cell-mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells

Publication date: Available online 6 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Hajime Suto, Aya Nambu, Hideaki Morita, Sachiko Yamaguchi, Takafumi Numata, Takamichi Yoshizaki, Eri Shimura, Ken Arae, Yousuke Asada, Kenichiro Motomura, Mari Kaneko, Takaya Abe, Akira Matsuda, Yoichiro Iwakura, Ko Okumura, Hirohisa Saito, Kenji Matsumoto, Katsuko Sudo, Susumu Nakae
BackgroundAs well as thymic stromal lymphopoietin (TSLP) and IL-33, IL-25 is known to induce Th2 cytokine production by various cell types—including Th2 cells, Th9 cells, invariant NKT cells and group 2 innate lymphoid cells—involved in Th2-type immune responses. Since both Th2-type and Th17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 may contribute to this by enhancing Th2-type immune responses. However, the precise role of IL-25 in the pathogenesis of FITC-induced CHS is poorly understood.ObjectiveWe investigated the contribution of IL-25 to CHS using Il25^-/- mice.MethodsCHS was evaluated by measurement of ear skin thickness in mice after FITC-painting. Skin dendritic cell (DC) migration, hapten-specific Th cell differentiation and detection of IL-1β-producing cells were determined by flow cytometry, ELISA and immunohistochemistry, respectively.ResultsIn contrast to TSLP, we found that IL-25 was not essential for skin DC migration or hapten-specific Th cell differentiation in the sensitization phase of CHS. Unexpectedly, mast cell- and non-immune cell-derived IL-25 was important for hapten-specific Th17 cell-, rather than Th2 cell-, mediated inflammation in the elicitation phase of CHS by enhancing Th17-related, but not Th2-related, cytokines in the skin. In particular, IL-1β produced by dermal DCs in response to IL-25 was crucial for hapten-specific Th17 cell activation, contributing to induction of local inflammation in the elicitation phase of CHS.ConclusionOur results identify a novel IL-25 inflammatory pathway involved in induction of Th17, but not Th2, cell-mediated CHS. IL-25 neutralization may be a potential approach for treatment of CHS.

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G3Fr06