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.  Secretory IgA binding to FCRL3 mAb diminishes the inhibitory capacity of regulatory T cells and promotes a Th17-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 IL-1ß, IL-6, IL-8, IL-10, IFN-?, and TNF-a protein secretion by both T cell types.  .    We propose that secretory IgA provokes in regulatory and effector T cells a coordinated inflammatory response to facilitate mucosal pathogen clearance. Overall design: We assessed the impact of secretory IgA (SIgA) and anti-FCRL3 mAb antibody stimulation on human CD4+ regulatory T cells and CD8+ effector T cells at two time points using bulk RNA-seq.   CD4+CD25hiCD127dim CD14- regulatory T cells and CD8+CD45RO-CCR7- terminal effector T cells were sorted from peripheral blood and stimulated with (1) biotinylated secretory lgA followed by streptavidin; (2) biotinylated FCRL3 mAb mAb followed by streptavidin; (3) streptavidin as control.                             Transcript abundances of secretory lgA and FCRL3 mAb mAb stimulated samples were compared with that of the control.