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Kathryne E Marks, Stephanie Flaherty, Joseph M Reynolds, Thpok suppresses pathogenic cytokine production by Th17 cells in autoimmune disease, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 115.19, https://doi.org/10.4049/jimmunol.202.Supp.115.19
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Abstract
CD4+ T cells, including Th17 cells, are instrumental in the development and progression of autoimmune diseases such as multiple sclerosis. While pathogenic Th17 cells drive inflammation in autoimmunity, the molecular programming underlying their pathogenicity remains insufficiently understood. Through RNA-sequencing, we have identified the transcription factor Thpok (Zbtb7b), also known as the CD4 lineage determination factor, as an apparent negative regulator of Th17 pathogenicity. Thpok expression is maintained in peripheral CD4+ T cells and assists in formation of memory CD4+ T cells. Furthermore, Thpok expression in CD4+ T cells represses cytotoxic genes and contributes to the Th17 response during intestinal inflammation. Herein we show Thpok is upregulated in pathogenic Th17 cells both in vitro and in vivo. In addition, we show increased expression of Thpok results in reduced production of IL-17, while conversely, loss of Thpok results in higher inflammatory potential of Th17 cells. Moreover, we have demonstrated that Thpok expression in Th17 cells in vivo functions to inhibit the development of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Altogether this study establishes Thpok as a suppressor of the autoimmune inflammatory function of Th17 cells.
