title: Insulin-like growth factor-2 enhances functions of antigen (Ag)-specific regulatory B cells.
abstract: Regulatory B cells (Bregs) are important in immune regulation. The factors that regulate Breg functions are less clear. Insulin-like growth factor 2 (IGF2) is capable of inducing hematopoietic stem cell differentiation. This study aimed to investigate the role of IGF2 in the development of Bregs and the enhancement of their function. In this study, the expression of IGF1 receptor (IGF1R) and IGF2R in ovalbumin (OVA)-specific B cells (OVAsBCs) was assessed by real time RT-PCR and Western blotting. The release of interleukin (IL)-10 from OVAsBCs and OVAsBC proliferation were assessed by enzyme-linked immunoassay and proliferation assay. The role of IGF2 in enhancing the function of OVAsBCs was tested with an intestinal allergic inflammation mouse model. The results showed that OVAsBCs expressed high levels of IGF2R. Exposure to both IGF2 and a specific antigen (Ag), OVA, markedly enhanced the expression of IL-10 in OVAsBCs as well as enhanced the IL-10(+) OVAsBC proliferation. The concurrent exposure to IGF2 and specific Ag markedly induced the IL-10 promoter DNA demethylation via activating the STAT5 pathway. IGF2 also enhanced both the OVAsBC proliferation in vivo and the effect of Ag-specific immunotherapy on inhibiting allergic inflammation in the intestine. We conclude that OVAsBCs express high levels of IGF2R and that IGF2 increases the expression of IL-10 in OVAsBCs and enhances OVAsBC proliferation and the inhibitory effect on allergic inflammation.
authors.affiliation: From the Otolaryngology Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen 518060, China, Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen 518116, China, and.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Geng
authors.affiliation: From the Otolaryngology Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen 518060, China, Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen 518116, China, and.
authors.forename: Gui
authors.initials: G
authors.lastname: Yang
authors.affiliation: From the Otolaryngology Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen 518060, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Jiang-Ping
authors.initials: JP
authors.lastname: Song
authors.affiliation: From the Otolaryngology Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen 518060, China, Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen 518116, China, and.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: From the Otolaryngology Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen 518060, China, Longgang Central Hospital, ENT Hospital, Shenzhen ENT Institute, Shenzhen 518116, China, and.
authors.forename: Shuqi
authors.initials: S
authors.lastname: Qiu
authors.affiliation: From the Otolaryngology Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen 518060, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: From the Otolaryngology Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen 518060, China, pcy2356@szu.edu.cn lzg@szu.edu.cn.
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000276:immunology; D017527:Receptor, IGF Type 2 / Q000235:genetics / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; C513121:IGF2 protein, mouse; C556062:IL10 protein, mouse; D017527:Receptor, IGF Type 2; D050799:STAT5 Transcription Factor; D016753:Interleukin-10; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1
keywords: Allergy; Immunology; Immunosuppression; Insulin-like Growth Factor (IGF); Mucosal Immunology