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The microRNA cluster miR-17~92 promotes TFH cell differentiation and represses subset-inappropriate gene expression

ABSTRACT: Follicular helper T cells (TFH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for TFH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17~92 was critical for robust differentiation and function of TFH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17~92 restrained the expression of genes M-bM-^@M-^XinappropriateM-bM-^@M-^Y to the TFH cell subset, including the direct miR-17~92 target Rora. Removal of one Rora allele partially M-bM-^@M-^XrescuedM-bM-^@M-^Y the inappropriate gene signature in miR-17~92-deficient TFH cells. Our results identify the miR-17~92 cluster as a critical regulator of T cellM-bM-^@M-^Sdependent antibody responses, TFH cell differentiation and the fidelity of the TFH cell gene-expression program. Gene expression analysis of control versus miR-17~92 knockout (KO) LCMV-specific SMARTA TFH cells 5.5 days after viral infection.

ORGANISM(S): Mus musculus

SUBMITTER: Dirk Baumjohann

PROVIDER: E-GEOD-42760 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The microRNA cluster miR-17~92 promotes TFH cell differentiation and represses subset-inappropriate gene expression

Project description:Follicular helper T cells (TFH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for TFH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17~92 was critical for robust differentiation and function of TFH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17~92 restrained the expression of genes ‘inappropriate’ to the TFH cell subset, including the direct miR-17~92 target Rora. Removal of one Rora allele partially ‘rescued’ the inappropriate gene signature in miR-17~92-deficient TFH cells. Our results identify the miR-17~92 cluster as a critical regulator of T cell–dependent antibody responses, TFH cell differentiation and the fidelity of the TFH cell gene-expression program.

2013-06-30 | GSE42760 | GEO

Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH)

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Germinal center T follicular helper cell IL-4 production is dependent on SLAM receptor (CD150)

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. This SuperSeries is composed of the following subset Series: GSE21379: Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH) GSE21380: Expression Data from in vivo Tfh vs GC Tfh vs non-Tfh Refer to individual Series

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