The role of CD69 molecule in the mucosal immune responses of the intestine
CD69 is highly expressed by lymphocytes at mucosal surfaces, but its role in immune responses is largely unknown. I aimed to investigate the role of CD69 in mucosal immune responses. The expression of CD69 by spleen, mesenteric lymph nodes, small intestinal and colonic lamina propria CD4 T cells was determined in specific pathogen free B6 and T cell receptor (TCR) transgenic mice and in germ-free B6 mice and intestinal microflora depleted TCR transgenic animals. Colitis was induced by transplanting RAG-/- mice with B6, CD69-/- or type I interferon receptor (IFNAR)-deficient CD45RBhigh CD4 T cells or by dextran sodium sulphate (DSS) treatment. CD69 expression by CD4 T cells is induced by the intestinal microflora, oral delivery of specific antigen or type I interfrons. CD69-/- CD4 T cells produce increased amounts of pro-inflammatory cytokines IFN-gamma, TNF-alpha and IL-21 and decreased amounts of regulatory cytokine TGF-ß1. Furthermore, CD69-deficient CD4 T cells show reduced potential to differentiate into Foxp3+ regulatory cells (Treg) in vivo and in vitro. The transfer of CD69-/- CD4 T cells into RAG-/- hosts or DSS administration to CD69-/- mice induce an accelerated colitis. CD69-/- CD4 T cells express higher levels of chemokine ligands and receptors and migrate more efficiently to the intestinal tissues in vivo compared to B6 cells. Oral tolerance is impaired in CD69-/- and IFNAR-/- mice comparing to B6 and OT-II x RAG-/- animals. Polyinosine polycytidylic acid (poly (I:C)) treatment of RAG-/- mice transplanted with B6 but not CD69-/- or IFNAR-/- CD4 T cells attenuate transfer colitis. In the line with this, CD69 deficiency on CD4 T cells affected poly (I:C)-induced IFN-ß1 expression. CD69 deficiency led to the increased production of pro-inflammatory cytokines and chemokines, reduced Foxp3+ Treg cell induction, impaired oral tolerance and more severe colitis. Hence, the activation antigen CD69 plays an important role in regulating mucosal immune responses.
Subject HeadingsDarmflora [GND]
Gastrointestinal tract; Immunology [MeSH]
Immunity, mucosal [MeSH]
Inflammatory bowel diseases; Immunology [MeSH]
Intestinal mucosa; Immunology [MeSH]