IL-25 enhances TH17 cell–mediated contact dermatitis by promoting IL-1? production by dermal dendritic cells - 06/11/18
Abstract |
Background |
In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce TH2 cytokine production by various cell types, including TH2 cells, TH9 cells, invariant natural killer T cells, and group 2 innate lymphoid cells, involved in TH2-type immune responses. Because both TH2-type and TH17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 can contribute to this by enhancing TH2-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 TH 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 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–mediated 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.
Conclusion |
Our results identify a novel IL-25 inflammatory pathway involved in induction of TH17 cell–mediated, but not TH2 cell–mediated, CHS. IL-25 neutralization can be a potential approach for treatment of CHS.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : IL-25, IL-33, thymic stromal lymphopoietin, contact hypersensitivity, gene-deficient mice, TH2, TH17
Abbreviations used : BM, BMDC, CHS, DC, DNFB, EPO, FITC, LN, MC, MPO, TSLP, WT
Plan
| Supported by Grants-in-Aid for Young Scientists (A and B; to S.N.); the Program for Improvement of Research Environment for Young Researchers, Special Coordination Funds for Promoting Science and Technology (to S.N.), from the Ministry of Education, Culture, Sports, Science and Technology, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency (to S.N.); a Health Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare, Japan (to H.S., S.N., and K.M.); and a grant from the Japan Chemical Industry Association Long-range Research Initiative (to S.N.). |
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| Disclosure of potential conflict of interest: H. Morita is employed by the National Research Institute for Child Health and Development. H. Saito received payment for lectures from Shiseido, MSD (Merck Sharp and Dohme), and AstraZeneca. K. Matsumoto is employed by the National Research Institute for Child Health and Development and received payment for lectures from MSD (Merck Sharp and Dohme), Kyorin Pharmaceutical, AstraZeneca, Maruho, Teijin Pharma, and Chugai Pharmaceutical. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 5
P. 1500 - novembre 2018 Retour au numéro
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