[PDF][PDF] An interleukin-33-mast cell-interleukin-2 axis suppresses papain-induced allergic inflammation by promoting regulatory T cell numbers

H Morita, K Arae, H Unno, K Miyauchi, S Toyama… - Immunity, 2015 - cell.com
H Morita, K Arae, H Unno, K Miyauchi, S Toyama, A Nambu, K Oboki, T Ohno, K Motomura
Immunity, 2015cell.com
House dust mite-derived proteases contribute to allergic disorders in part by disrupting
epithelial barrier function. Interleukin-33 (IL-33), produced by lung cells after exposure to
protease allergens, can induce innate-type airway eosinophilia by activating natural helper
(NH) cells, a member of group 2 innate lymphoid cells (ILC2), to secrete Th2 type-cytokines.
Because IL-33 also can induce mast cells (MCs) to secrete Th2 type-cytokines, MCs are
thought to cooperate with NH cells in enhancing protease or IL-33-mediated innate-type …
Summary
House dust mite-derived proteases contribute to allergic disorders in part by disrupting epithelial barrier function. Interleukin-33 (IL-33), produced by lung cells after exposure to protease allergens, can induce innate-type airway eosinophilia by activating natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2), to secrete Th2 type-cytokines. Because IL-33 also can induce mast cells (MCs) to secrete Th2 type-cytokines, MCs are thought to cooperate with NH cells in enhancing protease or IL-33-mediated innate-type airway eosinophilia. However, we found that MC-deficient KitW-sh/W-sh mice exhibited exacerbated protease-induced lung inflammation associated with reduced numbers of regulatory T (Treg) cells. Moreover, IL-2 produced by IL-33-stimulated MCs promoted expansion of numbers of Treg cells, thereby suppressing development of papain- or IL-33-induced airway eosinophilia. We have thus identified a unique anti-inflammatory pathway that can limit induction of innate-type allergic airway inflammation mediated by NH cells.
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