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Updated: May 28, 2026

In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse
07:46

In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse

Published on: October 25, 2024

α9β1 integrin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cell generation

Masashi Kanayama1, Junko Morimoto, Yutaka Matsui

  • 1Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.

Journal of Immunology (Baltimore, Md. : 1950)
|November 1, 2011
PubMed

The interaction between matricellular proteins such as tenascin-C (TN-C) and osteopontin (OPN) and integrins has been implicated in the pathology of rheumatoid arthritis in which Th17 cells are recognized as primary pathogenic cells. The differentiation of Th17 cells is tightly regulated by cytokines derived from APCs, receiving various signals including TLR stimuli. In this study, we used a collagen-induced arthritis model and found that increased numbers of α(9) integrin-positive conventional dendritic cells and macrophage were detectable in the draining lymph node (dLN) shortly following first immunization, and these cells produced both TN-C and OPN, ligands for α(9) integrin. α(9) integrin-mediated signaling, induced by TN-C and OPN, promoted the production of Th17-related cytokines by conventional dendritic cells and macrophages in synergy with TLR2 and 4 signaling. This led to the Th17 cell differentiation and arthritis development. Moreover, Th17 cells generated under blocking of α(9) integrin-mediated signaling showed low level of CCR6 expression and impaired migration ability toward CCL20. Thus, we have identified α(9) integrin-mediated signaling by TN-C and OPN as a novel intrinsic regulator of pathogenic Th17 cell generation that contributes to the development of rheumatoid arthritis.

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