Hueber, A. J., Asquith, D. L., Miller, A. M., Reilly, J., Kerr, S., Leipe, J., Melendez Romero, A. J. and McInnes, I. B. (2010) Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium. Journal of Immunology, 184(7), pp. 3336-3340. (doi: 10.4049/jimmunol.0903566) (PMID:20200272)
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Abstract
The proinflammatory cytokine IL-17A is considered a crucial player in rheumatoid arthritis (RA) pathogenesis. In experimental models of autoimmune arthritis, it has been suggested that the cellular source of IL-17A is CD4<sup>+</sup> T cells (Th17 cells). However, little is known about the source of IL-17 in human inflamed RA tissue. We explored the cellular sources of IL-17A in human RA synovium. Surprisingly, only a small proportion of IL-17–expressing cells were T cells, and these were CCR6 negative. Unexpectedly, the majority of IL-17A expression colocalized within mast cells. Furthermore, we demonstrated in vitro that mast cells produced RORC-dependent IL-17A upon stimulation with TNF-α, IgG complexes, C5a, and LPS. These data are consistent with a crucial role for IL-17A in RA pathogenesis but suggest that in addition to T cells innate immune pathways particularly mediated via mast cells may be an important component of the effector IL-17A response.
| Item Type: | Articles |
|---|---|
| Keywords: | BLOOD BREAST breast cancer BREAST-CANCER CANCER CELLS COLLAGEN-INDUCED ARTHRITIS CUTTING EDGE DISTINCT EXPRESSION Human IMMUNE inflammation INTERLEUKIN-17 JOINTS MODEL PATHWAY PHENOTYPE PROFILE RESPONSES RHEUMATOID-ARTHRITIS Scotland STIMULATION T cells T-cell T-CELLS TH17 CELLS |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Reilly, Mr James and Asquith, Dr Darren and Miller, Dr Ashley and Kerr, Mrs Shauna and Melendez Romero, Dr Alirio and Hueber, Dr Axel |
| Authors: | Hueber, A. J., Asquith, D. L., Miller, A. M., Reilly, J., Kerr, S., Leipe, J., Melendez Romero, A. J., and McInnes, I. B. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of Immunology |
| Publisher: | American Association of Immunologists |
| ISSN: | 0022-1767 |
| ISSN (Online): | 1550-6606 |
| Published Online: | 03 March 2010 |
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