IgA+ plasma cells in murine intestinal lamina propria as a positive regulator of Treg differentiation.
Continuous exposure to commensal bacteria gives rise to a complex intestinal immune system that maintains local tolerance, which requires Foxp3-expressing Treg. Recently, the regulation of TFH function by plasma cells has been reported, but effects of intestinal LP-PCs, one of the richest plasma cells in the body, on T cell differentiation have not been studied. Here, we investigated whether IgA(+) LP-PCs from murine small intestines had effects on T cell differentiation. Surprisingly, when IgA(+) LP-PCs were cocultured with CD4(+) T cells, Foxp3 expression was increased significantly in CD4(+)CD25(-) T cells. Results using the Transwell coculture system revealed that soluble factors from LP-PCs, TGF-β, and RA were involved in the induction of Foxp3 expression. Furthermore, Foxp3(+)CD25(-) T cells were decreased in PP after intestinal depletion of plasma cells. In addition, intestinal colony transfer from SPF to germ-free mice was demonstrated to generate IgA(+) LP-PCs and Foxp3(+) T cells with meaningful correlation in LP. We report for the first time that IgA(+) LP-PCs induce Foxp3 expression in T cells through TGF-β and RA. LP-PCs generated by commensal bacteria may play a crucial role in intestinal immunity through the induction of Treg, as well as IgA production.
1.School of Life Sciences and Biotechnology, Korea University, 5-ga, Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea. tskim@korea.ac.kr.
Myun Soo
MS
Kim
Tae Sung
TS
Kim
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D018920:Coculture Techniques; D005434:Flow Cytometry; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology
D007070:Immunoglobulin A
Foxp3; TGF-β; regulatory T cell; retinoic acid