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

Author:

Chu K-H1,Chiang B-L123

Affiliation:

1. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

2. Allergy Center, National Taiwan University Hospital, Taipei, Taiwan

3. Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan

Abstract

Summary 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 CD23loCD21loB 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.

Funder

National Health Research Institute, Republic of China

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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