期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 28, 页码 8708-8713出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1507625112
关键词
IL-4 receptor; eosinophil; macrophage; CD300f; inflammation
资金
- Morasha Program [1084/10]
- US-Israel Binational Science Foundation [2011244]
- Israel Science Foundation [955/11]
- Varda and Boaz Dotan Research Grant in Hemato-oncology
- Israel Cancer Research Association
- Fondo de Investigaciones Sanitarias [PI1100045]
- National Institute of Allergy and Infectious Diseases Intramural Research Program
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-4R alpha-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 alpha. Using Cd300f(-/-) cells and receptor cross-linking experiments, we established that CD300f amplified IL-4R alpha-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 alpha-induced immune cell responses. These data provide new insights into the molecular mechanisms governing IL-4R alpha-induced responses, and may provide new therapeutic tools to target IL-4 in allergy and asthma.
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