title: RBP-J is required for M2 macrophage polarization in response to chitin and mediates expression of a subset of M2 genes.
abstract: Development of alternatively activated (M2) macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP-J as an essential regulator of differentiation and function of alternatively activated macrophages.
authors.affiliation: Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY, 10021, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Foldi
authors.affiliation: School of Medicine and Institute for Immunology, Tsinghua University, Beijing, 100084, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY, 10021, USA.
authors.forename: Baohong
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY, 10021, USA. ivashkivl@hss.edu.|Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY, 10021, USA. ivashkivl@hss.edu.
authors.forename: Lionel B
authors.initials: LB
authors.lastname: Ivashkiv
authors.affiliation: School of Medicine and Institute for Immunology, Tsinghua University, Beijing, 100084, China. xiaoyuhu@tsinghua.edu.cn.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002686:Chitin / Q000276:immunology / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects* / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D002686:Chitin
keywords: M2; RBP-J; arginase; chitin; macrophages