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CD300f associates with IL-4 receptor ? and amplifies IL-4-induced immune cell responses.


ABSTRACT: IL-4 receptor (R) ?, the common receptor chain for IL-4 and IL-13, is a critical component in IL-4- and IL-13-mediated signaling and subsequent effector functions such as those observed in type 2 inflammatory responses. Nonetheless, the existence of intrinsic pathways capable of amplifying IL-4R?-induced responses remains unknown. In this study, we identified the myeloid-associated Ig receptor CD300f as an IL-4-induced molecule in macrophages. Subsequent analyses demonstrated that CD300f was colocalized and physically associated with IL-4R?. Using Cd300f(-/-) cells and receptor cross-linking experiments, we established that CD300f amplified IL-4R?-induced responses by augmenting IL-4/IL-13-induced signaling, mediator release, and priming. Consistently, IL-4- and aeroallergen-treated Cd300f(-/-) mice displayed decreased IgE production, chemokine expression, and inflammatory cell recruitment. Impaired responses in Cd300f(-/-) mice were not due to the inability to generate a proper Th2 response, because IL-4/IL-13 levels were markedly increased in allergen-challenged Cd300f(-/-) mice, a finding that is consistent with decreased cytokine consumption. Finally, CD300f expression was increased in monocytes and eosinophils obtained from allergic rhinitis patients. Collectively, our data highlight a previously unidentified role for CD300f in IL-4R?-induced immune cell responses. These data provide new insights into the molecular mechanisms governing IL-4R?-induced responses, and may provide new therapeutic tools to target IL-4 in allergy and asthma.

SUBMITTER: Moshkovits I 

PROVIDER: S-EPMC4507247 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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CD300f associates with IL-4 receptor α and amplifies IL-4-induced immune cell responses.

Moshkovits Itay I   Karo-Atar Danielle D   Itan Michal M   Reichman Hadar H   Rozenberg Perri P   Morgenstern-Ben-Baruch Netali N   Shik Dana D   Ejarque-Ortiz Aroa A   Hershko Alon Y AY   Tian Linjie L   Coligan John E JE   Sayós Joan J   Munitz Ariel A  

Proceedings of the National Academy of Sciences of the United States of America 20150629 28


IL-4 receptor (R) α, the common receptor chain for IL-4 and IL-13, is a critical component in IL-4- and IL-13-mediated signaling and subsequent effector functions such as those observed in type 2 inflammatory responses. Nonetheless, the existence of intrinsic pathways capable of amplifying IL-4Rα-induced responses remains unknown. In this study, we identified the myeloid-associated Ig receptor CD300f as an IL-4-induced molecule in macrophages. Subsequent analyses demonstrated that CD300f was col  ...[more]

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