IgA⁺ plasma cells in murine intestinal lamina propria as a positive regulator of T_reg differentiation

Continuous exposure to commensal bacteria gives rise to a complex intestinal immune system that maintains local tolerance, which requires Foxp3-expressing T_reg. Recently, the regulation of T_FH 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 T_reg, as well as IgA production.