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Cited by 301

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus

Open access
Shah, Kamini, Lee, Won-Woo, Lee, Seung-Hyun, Kim, Sang Hyun, Kang, Seong Wook, Craft, Joe, Kang, Insoo·2010·Arthritis Research & Therapy
DOI 10.1186/ar2964
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Abstract

Introduction: Interleukin (IL)-17 is a proinflammatory cytokine that is produced largely by a unique CD4+ T-helper (Th) subset called Th17 cells. The development of Th17 cells is suppressed by interferon (IFN)-γ produced by Th1 cells, suggesting cross-regulation between Th17 and Th1 cells. Thus, this study analyzed the balance of CD4+ Th17 and Th1 cell responses in peripheral blood from patients with systemic lupus erythematosus (SLE) and healthy subjects. Methods: Twenty-five adult patients with SLE and 26 healthy subjects matched for gender and age (± 2 years) were recruited. Peripheral blood mononuclear cells (PBMCs) from patients and healthy subjects were stimulated for 4 h ex vivo with phorbol myristate acetate (PMA) and ionomycin. The frequency of CD4+ T cells producing IL-17 and/or IFN-γ was measured by using flow cytometry. Expression of Th17-associated chemokine receptors CCR4 and CCR6 on CD4+ T cells as well as plasma levels of Th17-polarizing cytokines were assessed. Disease activity was evaluated by the SLE disease activity index score (SLEDAI). Unpaired t test and Pearson correlation were used for statistical analyses. Results: Patients with SLE had an increased frequency of CD4+IL-17+ T cells compared with healthy subjects. However, the frequency of CD4+IFN-γ+ T cells was similar between the two groups, indicating an altered balance of Th17 and Th1 cell responses in SLE. Patients with SLE also had an increased frequency of CD4+CCR4+CCR6+ T cells that are known to produce IL-17. The frequency of CD4+IL-17+ T cells and CD4+CCR4+CCR6+ T cells correlated with disease activity. In measuring plasma levels of the Th17-polarizing cytokines, levels of IL-6 were higher in patients with SLE than in healthy subjects, although levels of IL-1β, IL-21, IL-23, and transforming growth factor (TGF)-β were not different between the two groups. Conclusions: We demonstrate an enhanced Th17 cell response that correlates with disease activity in patients with SLE, suggesting a role for IL-17 in the pathogenesis of lupus. Our data indicate that the mechanisms involved in balancing Th1 and Th17 regulation, as well as in producing IL-6, are aberrant in SLE, leading to an increased Th17 response. We suggest that CCR4 and CCR6 expression on CD4+ T cells should be considered as markers of disease activity, and that IL-17 blocking may offer a therapeutic target in SLE.

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Metadata

Authors
Shah, K., Lee, W.-W., Lee, S.-H., Kim, S. H., Kang, S. W., Craft, J., & Kang, I.
Venue
Arthritis Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2010-03-24
Volume
12
Issue
2
Pages
R53-R53
ISSN
1478-6354 (ISSN-L)
DOI
10.1186/ar2964
OpenAlex
W2137266938
Cited by
301
References
41
FWCI
16.26
Type
journal article
Language
en
Open access
gold

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