Cutting Edge: Mast Cells Express IL-17A in Rheumatoid Arthritis Synovium

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)

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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794Institute of Infection Immunity and Inflammation