CD69 Is the Crucial Regulator of Intestinal Inflammation: A New Target Molecule for IBD Treatment?

Figure 3

The role of CD69 in mucosal immunity. Activation of intestinal CD4 T cell by antigen recognition, type I interferons (IFN-I), or by presence of intestinal microflora leads to the upregulation of CD69 expression on the cell surface. After binding a ligand, CD69 activates the intracellular pathways that result in decreased production of proinflammatory cytokines (IFN-γ, TNF-α, and IL-21) and chemokines (Ccl-1, Cxcl-10, and Ccl-19) and increased production of regulatory cytokine TGF-β1. If the CD4 T cell establishes a stable expression of CD69, this cell can differentiate into CD69⁺ regulatory T cell (Treg) or tissue resident memory T cell (T_RM). Therefore, upregulation of CD69 leads to the decreased migration of activated CD4 T cells to the intestine and to the increased regulatory responses, which ensures the establishment of oral tolerance and the attenuation of colitis severity.