title: CD300f associates with IL-4 receptor α and amplifies IL-4-induced immune cell responses.
abstract: 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.
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel;
authors.forename: Itay
authors.initials: I
authors.lastname: Moshkovits
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel;
authors.forename: Danielle
authors.initials: D
authors.lastname: Karo-Atar
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel;
authors.forename: Michal
authors.initials: M
authors.lastname: Itan
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel;
authors.forename: Hadar
authors.initials: H
authors.lastname: Reichman
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel;
authors.forename: Perri
authors.initials: P
authors.lastname: Rozenberg
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel;
authors.forename: Netali
authors.initials: N
authors.lastname: Morgenstern-Ben-Baruch
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel;
authors.forename: Dana
authors.initials: D
authors.lastname: Shik
authors.affiliation: Immunobiology Group, Centre d'Investigacions en Bioquímica i BiologiaMolecular en Nanomedicina-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona 08035, Spain;
authors.forename: Aroa
authors.initials: A
authors.lastname: Ejarque-Ortiz
authors.affiliation: Laboratory of Allergy and Clinical Immunology, Department of Medicine, The Herbert Center of Mast Cell Disorders, Meir Medical Center, Kfar Saba 44261, Israel;
authors.forename: Alon Y
authors.initials: AY
authors.lastname: Hershko
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Linjie
authors.initials: L
authors.lastname: Tian
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: John E
authors.initials: JE
authors.lastname: Coligan
authors.affiliation: Immunobiology Group, Centre d'Investigacions en Bioquímica i BiologiaMolecular en Nanomedicina-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona 08035, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Sayós
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel; arielm@post.tau.ac.il.
authors.forename: Ariel
authors.initials: A
authors.lastname: Munitz
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D007107:Immune System / Q000166:cytology / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology*; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism*; D008262:Macrophage Activation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000485:Allergens; C482560:CLM-1 protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit; D011971:Receptors, Immunologic; D015847:Interleukin-4; D007073:Immunoglobulin E
keywords: CD300f; IL-4 receptor; eosinophil; inflammation; macrophage