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TRAF3 regulates TFH cell differentiation during infections

ABSTRACT: TRAF3 regulates TFH cell differentiation during infections

PROVIDER: PRJNA1008096 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25735564_1.fastq.gz	Fastqsanger.gz
	SRR25735564_2.fastq.gz	Fastqsanger.gz
	SRR25735565_1.fastq.gz	Fastqsanger.gz
	SRR25735565_2.fastq.gz	Fastqsanger.gz
	SRR25735566_1.fastq.gz	Fastqsanger.gz

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Project description:TFH and Th1 cells generated after viral or intracellular bacterial infections are critical for the control of infections and the development of immunological memories. However, the mechanisms that govern the choice of activated CD4 T cells to the two alternative fates remain unclear. Here, we found that reciprocal expression of TCF1 and Blimp1 between viral-specific TFH and Th1 cells started early after infection. TCF1 was intrinsically required for the differentiation of TFH cells. In the absence of TCF1, TFH cells failed to maintain their transcriptional and metabolic signatures, distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1 signaling. Thus, we have demonstrated an essential role of TCF1 in TFH-cell differentiation. Tcf7 deficient and WT SMARTA CD4 T cells were isolated from mice 8 days after Lymphocytic Choriomeningitis Virus (LCMV) infection. TFH and Th1 cells were separated by FACS.

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Activin A regulates human T follicular helper (Tfh) cell differentiation

Project description:To determine the role of the cytokine activin A in the regulation of human T follicular helper (Tfh) cell gene program, we performed a transcriptomic analysis (RNA-seq) of human naÃ¯ve CD4 T cells differentiated in vitro with activin A. The analysis of the gene expression profile driven by activin A, alone or in combination with IL-12 (a know regulator of human Tfh differentiation/function), revealed that activin A can regulate the expression of multiple molecules involved in the differentiation and/or function of human Tfh cells. Human naÃ¯ve CD4 T cells were isolated from fresh PBMCs of healthy control subjects by magnetic bead isolation. Purity was measured by FACS as percentage of CD4+CD45RA+ cells and was 95% or higher. Upon isolation, naÃ¯ve CD4 T cells were stimulated with anti-CD3/CD28 coated beads in the presence of the following cytokine combinations: no exogenous cytokines (beads only), activin A, IL-12, activin A+IL-12, TGFb, TGFb +IL12. Following 5 days of in vitro culture, live CD4 T cells were FACS sorted and gene expression was analyzed by RNA-seq. Data are from independent donors.

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