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Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis.

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TLDR
It is shown that the increased frequency of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody, indicating the possible involvement of T fh cells in the disease progression of RA.
Abstract
Follicular helper T (Tfh) cells are recognized as a distinct CD4(+) helper T-cell subset, which provides for B-cell activation and production of specific antibody responses, and play a critical role in the development of autoimmune disease. So far, only one study investigated the circulating Tfh cells increased in a subset of SLE patients. Since relatively little is known about the Tfh cells in rheumatoid arthritis (RA) patients, in this study, Tfh-cell frequency, related cytokine IL-21, and transcription factor Bcl-6 were investigated in 53 patients with RA and 31 health controls. Firstly, we found that the frequency of CD4(+)CXCR5(+)ICOS(high) Tfh cells was increased significantly in the peripheral blood of RA patients, compared with that in healthy controls. It is known that Tfh cells are critical for directing the development of an antibody response by germinal centers B cells; secondly, we observed that the Tfh-cell frequency is accompanied by the level of anti-CCP antibody in RA patients. Furthermore, expression of Bcl-6 mRNA and plasma IL-21 concentrations in RA patients was increased. Taken together, these findings have shown that the increased frequency of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody, indicating the possible involvement of Tfh cells in the disease progression of RA.

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Journal ArticleDOI

The good, the bad and the ugly - TFH cells in human health and disease.

TL;DR: The elucidation of the mechanisms that regulate TFH cell differentiation, function and fate should highlight targets for novel therapeutics.
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Interleukin-21: a double-edged sword with therapeutic potential

TL;DR: An overview of the basic biology of IL-21 is provided and how this information has been — and can be — exploited therapeutically is discussed.
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Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis.

TL;DR: This review summarizes the current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.
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Cytokine-Mediated Regulation of Plasma Cell Generation: IL-21 Takes Center Stage

TL;DR: An overview of in vitro studies that evaluated the role of different cytokines in inducing the differentiation of distinct B-cell subsets to the PC lineage is provided, with particular emphasis on IL-21, which has emerged as the most potent inducer of terminal B- cell differentiation in humans.
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Human T follicular helper (Tfh) cells and disease

TL;DR: Recent studies have identified the circulating counterparts to tissue Tfh cells and with this has come a wealth of knowledge gained from the study of these cells in human disease.
References
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Journal ArticleDOI

Evolving concepts of rheumatoid arthritis

TL;DR: Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis.
Journal ArticleDOI

Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes.

TL;DR: The CD8+ effector cells raised in the CD4 subset- deficient host were able of clear vital tissues from productive infection and to restrict asymptomatic, persistent infection to acinar glandular epithelial cells in salivary gland tissue.
Journal ArticleDOI

IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways.

TL;DR: IL-6 orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-β, amplify RORγt-dependent differentiation of TH-17 cells.
Journal ArticleDOI

Bcl6 Mediates the Development of T Follicular Helper Cells

TL;DR: It is demonstrated that the transcription factor Bcl6 is both necessary and sufficient for TFH differentiation and subsequent B cell–mediated immunity, suggesting that it is a master regulator of this lineage.
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