Secretory IgA binding to FCRL3 triggers shared inflammatory cytokine secretion by human regulatory T cells and effector T cells.

Several human lymphocyte subsets express the novel secretory IgA receptor FCRL3 (Fc receptor-like 3). Secretory IgA binding to FCRL3 diminishes the inhibitory capacity of regulatory T cells and promotes a T helper 17-like phenotype. Here, we report that in CD4+ regulatory T cells and CD8+ terminal effector T cells secretory IgA induced a shared inflammatory gene signature that included PTGS2 encoding COX2, and the prototypic inflammatory cytokine genes IL1A, IL1B, and IL8. Secretory IgA in regulatory T cells also elevated gene transcripts required for lineage identity and function. Secretory IgA promoted interleukin (IL)-1β, IL-6, IL-8, IL-10, interferon γ, and tumor necrosis factor α protein secretion by both T cell types. Moreover, secretory IgA promoted NLRP3 inflammasome activation in regulatory T cells. Pharmacologic COX2 and NLRP3 inhibitors partially rescued the inhibitory competence of regulatory T cells, suggesting respective mechanistic roles. We propose that secretory IgA provokes a coordinated inflammatory response in regulatory and effector T cells to facilitate mucosal pathogen clearance.