Signal Transducers and Activators of Transcription

And KLF2 was also reported to suppress the transcription of by directly binding to its genomic region (36)

And KLF2 was also reported to suppress the transcription of by directly binding to its genomic region (36). but dispensable for regulating Tfh differentiation during protein immunization (32, 33). Apart from the grasp regulator Bcl-6, a network of several other transcription factors also participates in controlling the differentiation of Tfh cells during acute viral contamination. For example, it has been confirmed that through two different but complementary mechanisms, the transcription factor KLF2 (Krppel-like factor 2) functions to restrain Tfh cell generation. Lee et al. (35) found that KLF2 promotes the expression of the trafficking receptor S1PR1, the downregulation of which is essential for efficient Tfh cell differentiation. On the other hand, KLF2 favors the expression of several transcription factors that inhibit Tfh differentiation, such as Blimp1, Tbet, and GATA3. And KLF2 was also reported to suppress the transcription of by directly binding to its genomic region (36). Importantly, although Tbet is the grasp transcriptional regulator of Th1 cells, which were thought to inhibit Tfh cell differentiation, Tfh cells do exhibit medium to high levels of Tbet expression Lumicitabine in the LCMV contamination model (2). Recently, it has been reported that T-bet is usually virtually essential for the optimal expansion, proliferation, and maintenance of Tfh cells during acute viral contamination (37). Besides, Fang et al. (38) exhibited that at the early stage of CD4+ T cells response, the short-term expression of Tbet is critical for IFN- production in Th1-like Tfh cell subset. Additionally, transcription factors of the E-protein and Id families are well-appreciated for their role in T cell development. Shaw et al. (39) found that Tfh cells exhibited lower expression of Id2 than that of Th1 cells during acute viral contamination and knockdown of Id2 via shRNA increased the frequency of Tfh cells. Furthermore, Th1 differentiation was significantly blocked by the deficiency of gene during viral contamination. Ogbe et al. (40) found that EGR2 (early growth response gene 2) and EGR3 play a vital role in directing the expression of in Tfh cells. The differentiation of Tfh Lumicitabine cells was impaired in and deficient mice post viral contamination because of the defective expression of Bcl-6, resulting in a defective GC reaction and antibody production. Moreover, the overexpression of Bcl-6 in EGR2/3- deficient CD4+ T cells partially rescued the differentiation of Tfh cells and GC formation. Liu et al. (41) found that during influenza virus contamination, the deletion of Ascl2 in T cells results in impaired Tfh-cell development and germinal center response. Besides, in protein immunization or other contamination models, several other TFs have been confirmed to participate in the regulation of the fate commitment of Tfh cells. For example, c-Maf, IRF4, and Notch signaling pathway has been confirmed to promote Tfh differentiation while FOXO1 and FOXP1 inhibit Tfh fate commitment (21, 42C47). Besides networks mediated by transcriptional FAE factors, other different signaling pathways also control the differentiation and function of Tfh cells. Tfh cell differentiation are closely associated with mTOR-mediated Lumicitabine signaling pathways, which exert its effect by sensing and integrating environmental cues. During acute viral contamination, the interleukin-2 (IL-2)-mTORC1 signaling axis orchestrates the reciprocal balance between Th1 and Tfh cell fates by promoting Th1 while inhibiting Tfh cell differentiation (20). In contrast, it.

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