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Gene expression profile at single cell level of CD4 T cells from the spleens of wildtype (WT) and Interferon regulatory factor 5 (IRF5) knockout (KO) C57BL6/J mice following 6 hour anti-CD3/anti-CD28 stimulation

ABSTRACT: The precise mechanisms by which IRF5 regulates CD4 T cell support of the adaptive immune response is still unknown. Here, we used scRNAseq to analyse the impact of loss of Irf5 expression on CD4 T cells following T cell receptor (TCR) stimulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE267271 | GEO | 2024/09/18

REPOSITORIES: GEO

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Genome-wide maps of chromatin state of IRF5+/+ and IRF5-/- CD4+ mouse T cells

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Project description:RNA extracted from CD4 cells was analyzed using affymetrix gene array chips.Data set includes analysis of RNA from DMSO or ATRA treated samples. ATRA induced the expression of a number of genes including LZTFL1. Retinoic acids, which are metabolites of vitamin A, have been shown to be involved in multiple T cell effector responses through their binding to the retinoic acid receptor, a ligand-activated transcription factor. Because the molecular mechanism of regulation by retinoic acid is still not fully uncovered, we investigated the gene expression profile of all-trans retinoic acid (ATRA)-treated human CD4(+) T cells. Leucine zipper transcription factor-like 1 (LZTFL1) was upregulated by ATRA in a dose- and time-dependent manner. The expression of LZTFL1 depended on both ATRA and TCR signaling. LZTFL1 accumulated in the plasma membrane compartment of human CD4(+) T cells, and, during immunological synapse formation, it transiently redistributed to the T cell and APC contact zone, indicating its role in T cell activation. Live-cell imaging demonstrates that at the initial stage of immunological synapse formation, LZTFL1 is concentrated at the APC contact site, and, during later stages, it relocates to the distal pole. Knockdown of LZTFL1 reduced the basal- and ATRA-induced levels of IL-5 in CD4(+) T cells, and overexpression of LZTFL1 enhanced the TCR-mediated NFAT signaling, suggesting that LZTFL1 is an important regulator of ATRA-induced T cell response. Together, these data indicate that LZTFL1 modulates T cell activation and IL-5 levels. CD4 cells were isolated from human PBMCs and primed with anti-CD3 and IL-2 in presence and absence of retinoic acid. Two days later RNA was extracted and analyzed.

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