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Moshkovits, Itay; Karo-Atar, Danielle; Itan, Michal; Reichman, Hadar; Rozenberg, Perri; Morgenstern-Ben-Baruch, Netali; Shik, Dana; Ejarque-Ortiz, Aroa; Hershko, Alon Y; Tian, Linjie; Coligan, John E; Sayós, Joan; Munitz, Ariel
Proceedings of the National Academy of Sciences - PNAS, 07/2015, Letnik: 112, Številka: 28Journal Article
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 colocalized and physically associated with IL-4Ra. Using ... cells and receptor cross-linking experiments, we established that CD300f amplified IL-4Rα-induced responses by augmenting IL-4/IL-13-induced signaling, mediator release, and priming. Consistently, IL-4- and aeroallergen-treated ... mice displayed decreased IgE production, chemokine expression, and inflammatory cell recruitment. Impaired responses in ... 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 ... 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-4Rα-induced immune cell responses. These data provide new insights into the molecular mechanisms governing IL-4Ra-induced responses, and may provide new therapeutic tools to target IL-4 in allergy and asthma. (ProQuest: ... denotes formulae/symbols omitted.)
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