Abstract
Type 1 regulatory T (Tr1) cells can modulate inflammation through multiple direct and indirect molecular and cellular mechanisms and have demonstrated potential forĀ 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.
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Acknowledgments
A.A. received research support from 3M Corporation. W.H. received research support from MegaRobo Technologies Corporation. M.C.M. declares no competing financial interests. Research related to this review topic in the authorsā laboratories was supported in part by grants from the National Institutes of Health (R01AI120701, R01AI138570, R56AI146226, R21AI137822, P20GM130555-6610, R21AI129422, R21AI138497, and R35ES028244 (to Gary Perdew)). M.C.M. is a recipient of the Pathobiological Sciences Graduate Program Fellowship in the School of Veterinary Medicine at the Louisiana State University.
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McGee, M.C., August, A., Huang, W. (2021). TCR/ITK Signaling in Type 1 Regulatory T cells. In: Zheng, SG. (eds) T Regulatory Cells in Human Health and Diseases. Advances in Experimental Medicine and Biology, vol 1278. Springer, Singapore. https://doi.org/10.1007/978-981-15-6407-9_7
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