TCR/ITK Signaling in Type 1 Regulatory T cells.

Type 1 regulatory T (Tr1) cells can modulate inflammation through multiple direct and indirect molecular and cellular mechanisms and have demonstrated potential for anti-inflammatory therapies. Tr1 cells do not express the master transcription factor of conventional regulatory T cells, Foxp3, but express high levels of the immunomodulatory cytokine, IL-10. IL-2-inducible T-cell kinase (ITK) is conserved between mouse and human and is highly expressed in T cells. ITK signaling downstream of the T-cell receptor (TCR) is critical for T-cell subset differentiation and function. Upon activation by TCR, ITK is critical for Ras activation, leading to downstream activation of MAPKs and upregulation of IRF4, which further enable Tr1 cell differentiation and suppressive function. We summarize here the structure, signaling pathway, and function of ITK in T-cell lineage designation, with an emphasis on Tr1 cell development and function.