CD69: an unexpected regulator of TH17 cell-driven inflammatory responses

Abstract

Mice lacking the C-type lectin receptor CD69 develop exacerbated forms of arthritis, contact dermatitis, allergic asthma, and autoimmune myocarditis. Because the immune responses in these diseases are largely mediated by a balance between proinflammatory subsets of T effector cells called T helper (T(H)) 17 cells and regulatory T cells, these findings indicate a previously unappreciated regulatory role for CD69 in modulating T lymphocyte differentiation toward the T(H)17 lineage and suggest a role in regulatory T cell function. CD69 promotes activation of the Jak3-signal transducer and activator of transcription 5 (Stat5) signaling pathway, which inhibits T(H)17 cell differentiation, thus providing a mechanistic link between CD69 and the regulation of T(H)17 responses. This evidence underscores the potential of CD69 as target in the treatment of autoimmune and allergic diseases and is consistent with mounting evidence linking CD69 to regulatory T cell subsets.