Characterization and functional studies of forkhead box protein 3(-) lymphocyte activation gene 3(+) CD4(+) regulatory T cells induced by mucosal B cells.

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 T-reg-of-B(P) cells); however, it is important to characterize this particular subset of T-reg-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 T-reg-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 T-reg-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 T-reg-of-B cells with LAG3 expression, compared with CD23(lo)CD21(lo) B cells. LAG3 is not only a marker for T-reg-of-B(P) cells, but also participate in the suppressive ability. Moreover, CCR4 and CCR6 could be detected on the LAG3(+), not LAG3(-), T-reg-of-B(P) cells and would help cells homing to allergic lung. In the murine model of asthma, the adoptive transfer of LAG3(+) T-reg-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 T-reg-of-B(P) cells and was also involved in the function of T-reg-of-B(P) cells. In the future, this particular subset of T-reg-of-B cells might be used to alleviate allergic symptoms.