Impact of Tcf1 and Lef1 deficiency on follicular helper T (Tfh) cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE66781 | GEO | 2015/07/14
SECONDARY ACCESSION(S): PRJNA277948
REPOSITORIES: GEO
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Project description:The goal of this study is to determine the impact of Tcf1 and Lef1 deficiency on T follicular helper (Tfh) cells elicited by protein immunization. We demonstrate that although phenotypic Tcf1/Lef1-deficient Tfh cells were able to develop in response to vaccination, they are functionally impaired. Mechanisc studies reveal the direct regulatory effect by Tcf1 and Lef1 on transcriptome and chromatin accessibility in vaccine-elicited Tfh cells. Analysis of chromatin accessibility in WT and Tcf1/Lef1-deficient Tfh cells eliciated by vaccination.
2020-10-19 | GSE146421 | GEO
Project description:The goal of this study is to determine the impact of Tcf1 and Lef1 deficiency on T follicular helper (Tfh) cells elicited by protein immunization. We demonstrate that although phenotypic Tcf1/Lef1-deficient Tfh cells were able to develop in response to vaccination, they are functionally impaired. Mechanisc studies reveal the direct regulatory effect by Tcf1 and Lef1 on transcriptome and chromatin accessibility in vaccine-elicited Tfh cells.
2020-10-19 | GSE146422 | GEO
Project description:The goal of this study is to determine the impact of Tcf1 and Lef1 deficiency on T follicular helper (Tfh) cells elicited by protein immunization. We demonstrate that although phenotypic Tcf1/Lef1-deficient Tfh cells were able to develop in response to vaccination, they are functionally impaired. Mechanisc studies reveal the direct regulatory effect by Tcf1 and Lef1 on transcriptome and chromatin accessibility in vaccine-elicited Tfh cells.
2020-10-19 | GSE146425 | GEO
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) WT and Sh2d1a-/- follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.
2010-04-28 | E-GEOD-21379 | biostudies-arrayexpress
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.
2015-09-18 | E-GEOD-65660 | biostudies-arrayexpress
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
2010-04-20 | GSE21379 | GEO
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.
2015-09-18 | GSE65660 | GEO
Project description:T follicular helper cells (TFH) are heterogenic population of CD4+ T cells, expressing CXCR5+ and PD-1+ on their surface. Their role is linked to supporting formation of germinal centres (GC) and these cells are thought to express high levels of PD-1 marker. Two models of immunisation were used to investigate the role of PD-1 low TFH. In Salmonella enterica infection high frequency of T follicular helper cells expressing low levels of PD-1 surface molecule are observed within first week of infection but GC do not appear until much a later stage (week 7-8). Sheep red blood cell immunisation (SRBC) gives rise to both TFH and GC B cells within first week of response and these TFH express low to high level of PD-1 molecule. Microarray analysis was applied in order to investigate the relationship between and characteristics of different TFH populations in order to elucidate their role in GC support, developmental stage and contributions to memory T cell pool.
2015-12-25 | GSE62961 | GEO
Project description:Comparison of transcriptome between GFP-RV+ Th1 cells and Lef1-RV+ Th1 cells B6 mice received GFP-RV+ or Lef1-RV+ LCMV gp specific TCRtg Smarta cells and were infected with LCMV. On four days after infection, splenocytes were collected to sort CXCR5- Th1 cells per genotype. Contributor: LIAI RNAi Center (LIAI)
2015-07-27 | E-GEOD-67335 | biostudies-arrayexpress
Project description:Comparison of epigenome and Tcf1 occupancy between control and Tcf1/Lef1-deficient CD8 T cells Control mice or those are deficient for Tcf1 and Lef1 transcription factors (deleted by CD4-Cre) were used to isolate thymocytes. The thymocytes were surface-stained to identify TCRbeta high, CD69â, CD24â CD8+ subsets. These cells were sorted for ChIPseq analysis of various histone marks. Control mice or those are deficient for Tcf1 (deleted by CD4-Cre) were used to isolate thymocytes. The splenocytes were surface-stained to identify TCRbeta high, CD8+ subsets. These cells were sorted for ChIPseq analysis of Tcf1 binding locations.
2016-02-12 | E-GEOD-73239 | biostudies-arrayexpress