IgA plasma cells express the negative regulatory co-stimulatory molecule programmed cell death 1 ligand and have a potential tolerogenic role in the intestine

To maintain immune homeostasis in the intestine, the intestinal immune system has evolved several tolerogenic mechanisms toward intestinal microflora and food antigens. Although programmed cell death-1 (PD-1) protein has been implicated in immunological tolerance in the intestine and gut-associated lymphoid tissues (GALTs), distribution of its ligands PD-L1 and PD-L2 in the small intestine lamina propria (LP) are unknown. We investigated PD-L1 expression in intestinal LP and found that IgA plasma cells (PCs) were major PD-L1 expressing cells. PD-L1 expression levels on IgA PCs were higher than that on IgG PCs in peripheral lymphoid tissues. IgA PCs expressed antigen-presenting molecule MHC class II and co-stimulatory molecules CD80, CD86, and PD-L2. IgA PCs isolated from intestinal LP exhibited antigen presentation activity, and in the presence of TGF-β induced FoxP3+ regulatory T cells, but not IFN-γ+ Th1 cells, from naïve T cells. Thus, IgA PCs in the intestine may be involved in an immune regulatory role in the intestinal immune system.

► IgA PCs are major PD-L1+ cells in the intestine. ► IgA PCs are potent inducer of CD4+ FoxP3+ Treg cells in the intestine. ► PD-L1 expression on IgA PCs is higher than that on peripheral IgG1 PCs.