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

I Moshkovits, D Karo-Atar, M Itan… - Proceedings of the …, 2015 - National Acad Sciences
I Moshkovits, D Karo-Atar, M Itan, H Reichman, P Rozenberg, N Morgenstern-Ben-Baruch
Proceedings of the National Academy of Sciences, 2015National Acad Sciences
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 …
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-4Rα. Using Cd300f−/− 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 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-4Rα–induced immune cell responses. These data provide new insights into the molecular mechanisms governing IL-4Rα–induced responses, and may provide new therapeutic tools to target IL-4 in allergy and asthma.
National Acad Sciences