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Toll-like receptor 2 induces pathogenicity in Th17 cells and reveals a role for IPCEF in regulating Th17 cell migration.

ABSTRACT: Pathogenic Th17 cells drive inflammation in autoimmune disease, yet the molecular programming underlying Th17 cell pathogenicity remains insufficiently understood. Activation of Toll-like receptor 2 (TLR2) increases Th17 cell inflammatory potential, but little is known regarding the mechanistic outcomes of TLR2 signaling in Th17 cells. Here, we demonstrate that TLR2 is comparable to IL-23 in inducing pathogenicity and increasing the migratory capacity of Th17 cells. We perform RNA sequencing of Th17 cells stimulated though the TLR2 pathway and find differential expression of several genes linked with the Th17 genetic program as well as genes not previously associated with pathogenic Th17 cells, including Ipcef1. Enforced expression of Ipcef1 in Th17 cells abolishes the TLR2-dependent increases in migratory capacity and severely impairs the ability of Th17 cells to induce experimental autoimmune encephalomyelitis. This study establishes the importance of the TLR2 signaling pathway in inducing Th17 cell pathogenicity and driving autoimmune inflammation.

SUBMITTER: Marks KE

PROVIDER: S-EPMC8270556 | biostudies-literature |

REPOSITORIES: biostudies-literature

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GATA3 induces the pathogenicity of Th17 cells via regulating GM-CSF expression.

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Project description:To investigate the effects of a late deletion of Gata3 on CD4 T cell gene expression profiles in experimental autoimmune encephalomyelitis, we performed a RNA-Seq analysis of Gata3-sufficient (i.e., Cd45.1/Cd45.2 or vehicle treated Cd45.2/Cd45.2 Cre-ERT2 Gata3 fl/fl) and Gata3-deficient (i.e., tamoxifen-treated Cd45.2/Cd45.2 Cre-ERT2 Gata3 Fl/Fl) CNS-infiltrating CD4+ effector T cells from mixed congenic co-transfer recipient mice. We performed a gene expression profiling analysis using data obtained from RNA-seq from 2 mixed congenic adoptive transfer receipient vehicle-treated mice and 2 mixed congenic adoptive transfer receipient tamoxifen-treated mice for a total of 8 biological samples.

2023-06-20 | GSE227394 | GEO

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