Does IL-21 produced in Peyer's patch regulate the affinity of IgA and food allergy?

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Dokkyo Medical University
• Principal Investigator: Hashiguchi Masaaki 獨協医科大学, 医学部, 准教授 (20372443)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: IgA / パイエル板 / IL-21

Outline of Final Research Achievements

IgA is at least partly induced in Peyer’s patches (PPs), which are secondary lymphoid tissues and scatteredly located in the small intestine (SI). However, the precise mechanisms have not been clarified yet. Establishing hybridomas from naive murine PPs revealed the major specificity against double stranded DNA in IgA. The IgA was induced by the intestinal microbes and in PPs, but was independent of CD4+ T cells. IgA positively regulate intestinal bacteria via an antigen-independent manner. TGF-beta induced IgA secretion from naive B cells, but was not enough for the induction of surface IgA. The additional IL-21 and IL-5 upregulate surface IgA+ B cell frequency. The blocking of IL-21R signaling abrogated GC B cell frequency and IgA+ B cells in PPs. PPs were required for oral antigen-specific IgA in the intestine. These results suggest that PPs are required for anti-dsDNA and anti-diet protein IgAs, and that IL-21 and IL-5 coordinately induce IgA.

Free Research Field

食品科学

Academic Significance and Societal Importance of the Research Achievements

腸管で産生されるIgA抗体については、一部は腸内細菌に結合するなど、特異性などが徐々に明らかにされつつあるが、詳細な解析は行われてきていなかった。本研究の結果は、IgA抗体の特異性を明らかにしたことにより全体像が見え、解析の方向性を定める点で、重要な知見となったと考える。また、IgA抗体産生誘導機構の一部が明らかとなり、今後の解析の上で重要な知見となったと考える。