Toll-like Receptor 2 Induces Pathogenicity in Th17 Cells and Reveals a Role for IPCEF in Regulating Th17 Cell Migration

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Jun 30

PMID 34192530

Citations 13

Authors

Kathryne E Marks

Stephanie Flaherty

Kristen M Patterson

Matthew Stratton

Gustavo J Martinez

Joseph M Reynolds

Affiliations

Soon will be listed here.

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.

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