Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Chronic Inflammatory Responses in Rheumatoid Arthritis: The Vicious Circle Might Be Related to Interaction of Th17 Cells with FLS or Mesenchymal Stem Cells.
Eljaafari1, Assia, Tartelin1, Marie-Laure, Miossec2, Pierre
TH17 cells have been involved in the initiation and maintenance of several inflammatory and autoimmune diseases, such as Rheumatoid Arthritis (RA). More recently, they gained further interest, due to the demonstration of their involvement in anti-tumor responses.
Here we postulated that if TH17 cells play a so preponderant role in inflammatory diseases, their development might be facilitated in this context. Therefore, using RA as a model of chronic inflammation, we hypothesized that interaction of T cells with mesenchymal cells, such as synoviocytes (FLS), or mesenchymal stem cells (MSC) could participate in the activation of the TH17 pathway, with the help of the inflammatory environment.
To investigate this possibility, mononuclear cells (MNC) from healthy blood donors were co-cultured with MSC from healthy controls, or FLS from either RA or osteoarthritic (OA) patients, and were activated with PHA or A/CD3+CD28 mABs, for 1 to 2 days. IL17A, TNFa, and or/IFNg were added or not to these co-cultures. Q-RT-PCR, ELISA,and cytoflurometry technics were used to assess for IL17-A production.
We observed that the interaction of MNC with healthy MSC resulted in an extinction of TH1 and TH2 cell activation, but was sufficient by its own to induce a strong production of TH17 cells, as soon as 24 hours post-activation, as assessed by the increase of IL17A at the mRNA and protein levels and by Th17 staining.The levels of IL17A further increased at 48 hours, and/or in the presence of IL17A, TNFa, and or/IFNg. IL6, IL8, and IL1 mRNA levels increased as well. Interestingly, co-culture with FLS from either OA or RA patients, also resulted in a strong induction of IL17, but not in TH1 inhibition. Finally, TH17 production was partially inhibited in the presence of anti-IL6 mAbs, or CTLA4-Ig fusion molecules, demonstrating thus the roles of IL6 and costimulatory molecules in such a production.
We show herein, that interaction of MSC,or FLS from RA or OA patients, with MNC results in enhancing the inflammatory response, through production of IL-17, IL6, IL-8 and IL-1 cytokines. Moreover, in the context of an inflammatory environment, i.e: presence of IL-17A, TNFa, and/or IFNg, such an interaction of T cells with MSC results in further amplifying the induction of TH17 cells, leading thus to a vicious circle, that may participate to the chronicity of inflammation.
To cite this abstract, please use the following information:
Eljaafari, Assia, Tartelin, Marie-Laure, Miossec, Pierre; Chronic Inflammatory Responses in Rheumatoid Arthritis: The Vicious Circle Might Be Related to Interaction of Th17 Cells with FLS or Mesenchymal Stem Cells. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1247