Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2018 May 27

PMID 29802020

Citations 84

Authors

Keiji Hirota

Motomu Hashimoto

Yoshinaga Ito

Mayumi Matsuura

Hiromu Ito

Masao Tanaka

Hitomi Watanabe

Gen Kondoh

Atsushi Tanaka

Keiko Yasuda

Manfred Kopf

Alexandre J Potocnik

Brigitta Stockinger

Noriko Sakaguchi

Shimon Sakaguchi

Affiliations

Soon will be listed here.

Abstract

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention.

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