09:30 - 12:10
Room: Ishikawa Ongakudō Hogaku Hall
Symposium
Chair/s:
Chen Dong, Vijay K. Kuchroo
An inflammatory cellular cascade of autoimmune Th17 cells, GM-CSF-producing synovial ILCs and stromal cells in autoimmune arthritis
Shimon Sakaguchi1, Keiji Hirota2
1Osaka University, Immunology Frontier Research Center, Osaka, Japan, 2Kyoto University, Institute for Frontier Life and Medical Sciences, Kyoto, Japan

Despite the key rolesimportance of Th17 cells in autoimmune diseases, it remains unclear how they control tissue-residentother inflammatory cells in autoimmune tissue damage. Using a mouse model (SKG mice) of spontaneous Th17 cell-mediated autoimmune arthritis, we showed that arthritogenic IL-17-producing Th17 cells stimulated fibroblast-like synoviocytes (FLS) via IL-17 to secrete 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 such as FLS prevented Th17 cell-mediated arthritis. In contrast, GM-CSF production by Th17 cells was not mandatory. Together with the presence of GM-CSF-producing ILCs in inflamed joints of rheumatoid arthritis patients, these results indicate that a cellular cascade of autoimmune IL-17-producing Th17, ILCs and non-lymphoid stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention.


Reference:
Tu-S2-5
Session:
Symposium 2, “Autoimmunity, chronic inflammation and cytokines”
Presenter/s:
Shimon Sakaguchi
Presentation type:
Invited Speaker
Room:
Ishikawa Ongakudō Hogaku Hall
Chair/s:
Chen Dong, Vijay K. Kuchroo
Date:
Tuesday, 31 October 2017
Time:
11:10 - 11:35
Session times:
09:30 - 12:10