title: Characterization and functional studies of forkhead box protein 3(-) lymphocyte activation gene 3(+) CD4(+) regulatory T cells induced by mucosal B cells.
abstract: The induction of mucosal tolerance has been demonstrated to be an effective therapeutic approach for the treatment of allergic diseases. Our previous study demonstrated that Peyer's patch B cells could convert naive T cells into regulatory T cells (so-called Treg -of-B(P) cells); however, it is important to characterize this particular subset of Treg -of-B cells for future applications. This study aimed to investigate the role of lymphocyte activating gene 3 (LAG3) in mediating the regulatory function of Treg -of-B(P) cells induced by mucosal follicular B (FOB) cells. Microarray analysis and real-time polymerase chain reaction (PCR) were used to assess the gene expression pattern of Treg -of-B(P) cells. To evaluate the role of LAG3, the in-vitro suppressive function and the alleviation of airway inflammation in a murine model of asthma was assessed. Our data indicated that FOB cells isolated from Peyer's patches had the ability to generate more suppressive Treg -of-B cells with LAG3 expression, compared with CD23(lo) CD21(lo) B cells. LAG3 is not only a marker for Treg -of-B(P) cells, but also participate in the suppressive ability. Moreover, CCR4 and CCR6 could be detected on the LAG3(+) , not LAG3(-) , Treg -of-B(P) cells and would help cells homing to allergic lung. In the murine model of asthma, the adoptive transfer of LAG3(+) Treg -of-B(P) cells was able to sufficiently suppress T helper type 2 (Th2) cytokine production, eosinophil infiltration and alleviate asthmatic symptoms. LAG3 was expressed in Treg -of-B(P) cells and was also involved in the function of Treg -of-B(P) cells. In the future, this particular subset of Treg -of-B cells might be used to alleviate allergic symptoms.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: K-H
authors.initials: KH
authors.lastname: Chu
authors.forename: B-L
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001249:Asthma / Q000235:genetics / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology*; D054398:Receptors, CCR4 / Q000235:genetics / Q000276:immunology; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology; D017464:Receptors, Complement 3d / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C498126:CCR6 protein, mouse; C515355:Ccr4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse
keywords: airway hyperresponsiveness; mucosal tolerance