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

• DOI: 10.1016/j.immuni.2018.04.009
• Publication Date: 2018-05-22T14:43:05Z
• 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. Poto...; Brigitta Stockinger; Noriko Sakaguchi; Shimon Sakaguchi
• Keywords: 0301 basic medicine; SKG; Synovial Membrane; autoimmunity; innate lymphoid cells; GM-CSF; Th17; IL-17; ILCs; innate lymphoid cells; autoimmunity; arthritis; SKG; Granulocyte-Macrophage Colony-Stimulating Factor; ILCs; GM-CSF; Article; Autoimmune Diseases; 3. Good health; Arthritis, Rheumatoid; Mice; IL-17; 03 medical and health sciences; arthritis; Animals; Humans; Th17 Cells; Lymphocytes; Th17; Stromal Cells

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.<br/>ISSN:1097-4180<br/>ISSN:1074-7613<br/>Immunity, 48 (6)<br/>