| First Author | Moshkovits I | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 28 | Pages | 8708-13 |
| PubMed ID | 26124135 | Mgi Jnum | J:223721 |
| Mgi Id | MGI:5660125 | Doi | 10.1073/pnas.1507625112 |
| Citation | Moshkovits I, et al. (2015) CD300f associates with IL-4 receptor alpha and amplifies IL-4-induced immune cell responses. Proc Natl Acad Sci U S A 112(28):8708-13 |
| abstractText | IL-4 receptor (R) alpha, 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-4Ralpha-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-4Ralpha. Using Cd300f(-/-) cells and receptor cross-linking experiments, we established that CD300f amplified IL-4Ralpha-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-4Ralpha-induced immune cell responses. These data provide new insights into the molecular mechanisms governing IL-4Ralpha-induced responses, and may provide new therapeutic tools to target IL-4 in allergy and asthma. |
