Interleukin-21 modulates Th1 and Th17 responses in giant cell arteritis.

Authors: Terrier, B  Geri, G  Chaara, W  Allenbach, Y  Rosenzwajg, M  Costedoat-Chalumeau, N  Fouret, P  Musset, L  Benveniste, O  Six, A  Klatzmann, D  Saadoun, D  Cacoub, P 
Citation: Terrier B, etal., Arthritis Rheum. 2012 Jun;64(6):2001-11. doi: 10.1002/art.34327. Epub 2011 Dec 6.
Pubmed: (View Article at PubMed) PMID:22147555
DOI: Full-text: DOI:10.1002/art.34327

OBJECTIVE: Giant cell arteritis (GCA) is a large-vessel vasculitis of unknown origin. Recent findings indicate that at least 2 separate lineages of CD4+ T cells, Th1 and Th17 cells, participate in vascular inflammation. The pathways driving these T cell differentiations are incompletely understood, but may provide novel therapeutic targets. This study was undertaken to identify cytokines involved in the pathogenesis of GCA. METHODS: Thirty GCA patients fulfilling the American College of Rheumatology criteria, with active disease or disease in remission, and 30 age-matched controls were included. Levels of 27 cytokines were determined in culture supernatants, and flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and immunohistochemical analysis of temporal artery samples were performed. RESULTS: Multiparametric analysis of cytokines produced by PBMCs associated with GCA disease activity identified a signature involving interleukin-2 receptor (IL-2R), IL-12, interferon-gamma (IFNgamma), IL-17A, IL-21, and granulocyte-macrophage colony-stimulating factor (GM-CSF). An expansion of Th1 and Th17 cells and a decrease in Treg cells were observed in the peripheral blood of patients with active GCA. An expansion of IL-21-producing CD4+ T cells was also observed in patients with active GCA and correlated positively with Th17 and Th1 cell expansion. Immunohistochemical analysis revealed IFNgamma, IL-17A, and IL-21 expression within inflammatory infiltrates. Stimulation of purified CD4+ T cells with IL-21 increased Th1 and Th17 cell frequencies and decreased FoxP3 expression. In contrast, blockade of IL-21 using IL-21R-Fc markedly decreased the production of IL-17A and IFNgamma and increased FoxP3 expression. CONCLUSION: Our findings indicate that IL-21 plays a critical role in modulating Th1 and Th17 responses and Treg cells in GCA, and might represent a potential target for novel therapy.

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CRRD Object Information
CRRD ID: 6892962
Created: 2012-08-21
Species: All species
Last Modified: 2012-08-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.