IL-25 enhances TH17 cell–mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells

Publication date: November 2018

Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5

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

Background

In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce T_H2 cytokine production by various cell types, including T_H2 cells, T_H9 cells, invariant natural killer T cells, and group 2 innate lymphoid cells, involved in T_H2-type immune responses. Because both T_H2-type and T_H17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 can contribute to this by enhancing T_H2-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_H 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_H cell differentiation in the sensitization phase of CHS. Unexpectedly, mast cell– and non–immune cell–derived IL-25 was important for hapten-specific T_H17 cell–mediated rather than T_H2 cell–mediated inflammation in the elicitation phase of CHS by enhancing T_H17-related, but not T_H2-related, cytokines in the skin. In particular, IL-1β produced by dermal DCs in response to IL-25 was crucial for hapten-specific T_H17 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 T_H17 cell–mediated, but not T_H2 cell–mediated, CHS. IL-25 neutralization can be a potential approach for treatment of CHS.

Graphical abstract

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