Constitutively altered frequencies of circulating follicullar helper T cell counterparts and their subsets in rheumatoid arthritis

Arroyo-Villa, Irene; Bautista-Caro, María-Belén; Balsa, Alejandro; Aguado-Acín, Pilar; Bonilla-Hernán, María-Gema; Plasencia, C.; Villalba, A.; Nuño, Laura; Puig‐Kröger, Amaya; Martı́n-Mola, Emilio; Miranda-Carús, María-Eugenia

doi:10.1186/s13075-014-0500-6

Cited by 80 publications

(74 citation statements)

References 37 publications

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“…Second, higher levels of IL-21 mRNA transcripts in RA patient peripheral blood mononuclear cells (PBMCs) from RA patients and higher levels of serum IL-21 are correlated positively with the scores of 28-joint count disease activity score (DAS28) and the levels of serum anti-CCP antibodies in patients with RA [4,25]. Although the expression of inhibitory receptors (such as CD200) can be important for the role of TFH cells in the pathogenesis of RA [26], an increased frequency of CD4 + CXCR5 + ICOS + T cells and a higher ratio of circulating CXCR5 + (Th2+Th17-like) to Th1-like cells in active RA patients, but no difference in the frequency of CD4 + CXCR5 + T cells, are detected between the patients and healthy controls [23]. Therefore, a higher frequency of different subsets of circulating TFH cells may be crucial for the development of RA and correlated closely with disease severity.…”

Section: Tfh Cells In Ramentioning

confidence: 81%

“…Furthermore, the concentrations of serum IL-21 in RA patients are significantly higher than that in healthy controls [25]. Functionally, circulating TFH cells can be divided into three subsets [22,23]. Among these, CXCR5 + Th2-like cells promote IgG and IgE secretion and CXCR5 + Th17-like cells promote IgG and, in particular, IgA secretion, while CXCR5 + Th1-like cells have little capacity to help B cells [22,23].…”

Section: Circulating Tfh Cellsmentioning

confidence: 96%

“…However, there are some differences between circulating TFH and GC TFH cells. Notably, circulating CD4 + CXCR5 + TFH cells express low levels of Bcl-6 but high levels of transcription factor Maf, which upregulates CXCR5 and IL-21 expression [23,24]. It is possible that Bcl-6 is necessary for TFH differentiation while the Maf is crucial for the maintenance of circulating TFH cells [24].…”

Section: Circulating Tfh Cellsmentioning

confidence: 98%

“…Functionally, circulating TFH cells can be divided into three subsets [22,23]. Among these, CXCR5 + Th2-like cells promote IgG and IgE secretion and CXCR5 + Th17-like cells promote IgG and, in particular, IgA secretion, while CXCR5 + Th1-like cells have little capacity to help B cells [22,23]. CXCR5 + Th2-like cells and CXCR5 + Th17-like cells dominate in patients with RA, and the ratios of CXCR5 + (Th2+ Th17-like cells) to Th1-like cells are correlated closely with disease severity in RA patients [23].…”

Section: Circulating Tfh Cellsmentioning

confidence: 99%

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Follicular helper T cells in rheumatoid arthritis

Cavero

Liao

et al. 2015

Clin Rheumatol

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in the joints and other tissues. Rheumatoid factor (RF) and anticyclic citrullinated peptides (anti-CCP) are biomarkers for the evaluation of RA although their functions in the pathogenesis of RA are poorly understood. CXC-chemokine receptor 5 (CXCR5)(+) T follicular helper (TFH) cells are essential for B cell maturation and antibody production. Recent studies have showed that dysregulated TFH cells are associated with the development of autoimmune diseases. This article reviews the characters and functions of TFH cells, such as their differentiation, expression, transcription factor, and B cell maturation. Meanwhile, we also discuss the possible mechanisms underlying the role of these cells in RA and potential treatments, including antibody-blocking agents, gene therapies, T cell vaccines, and T follicular regulatory (TFR) cells. Overall, we discuss the roles of TFH cells in the pathogenesis of RA and potential therapies for RA.

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Section: Tfh Cells In Ramentioning

confidence: 81%

Section: Circulating Tfh Cellsmentioning

confidence: 96%

Section: Circulating Tfh Cellsmentioning

confidence: 98%

Section: Circulating Tfh Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Follicular helper T cells in rheumatoid arthritis

Cavero

Liao

et al. 2015

Clin Rheumatol

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show abstract

“…Regarding Tregs, there appears to be a general agreement that these cells are enriched in synovial fluid in RA [19][20][21]; however, results for peripheral blood are conflicting [19]. Likewise, results regarding the proportions of TFh in RA are contradictory [22,23].…”

Section: Introductionmentioning

confidence: 95%

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Pandya

Lundell

Hallström

et al. 2016

Journal of Leukocyte Biology

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The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25 CD127 and also FOXP3 CXCR5 cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4CXCR3 (Th2 and Th17), CTLA4 and FOXP3 subsets were present in significantly higher frequencies, whereas CCR4 (Th1/Th17, CCR6CCR4CXCR3, and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4CXCR3 T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.

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T follicular helper (Tfh) cells in lupus: Activation and involvement in SLE pathogenesis

2016

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Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease characterized by a breakdown of tolerance to self. The autoantibodies generated in SLE are directed against nuclear components, with which they form immune complexes (ICs). ICs play key roles in organ and tissue damage, as well as in the activation of the innate and adaptive immune system during the disease course. Therefore, it is of prime importance to understand the mechanisms responsible for the development of B cells producing these pathogenic autoantibodies. There is compelling evidence that T follicular helper (Tfh) cells play a fundamental role in this process. In this review, we will summarize the current knowledge regarding the involvement of Tfh cells in SLE pathogenesis, and discuss potential strategies to target Tfh cells and/or molecules as a therapeutic modality of SLE.Keywords: Autoantibody r B cell r Systemic lupus erythematosus (SLE) r Tfh cell IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a loss of tolerance toward nuclear components, leading to autoantibody production, immune complex formation and organ and tissue damage. Described more than 150 years ago primarily as a skin disorder affecting women in the "prime of life", it was soon recognized that the disease could adopt a systemic course and carry a serious prognosis, "its termination being frequently fatal to life" [1]. In the final years of the 19th century and over the 20th century, many of the recognizable features, as well as the clinical heterogeneity of the disease, were described [2]. Human lupus in fact presents with a spectrum of clinical manifestations ranging from solely skin involvement (cutaneous lupus erythematosus) to a systemic disease (SLE), the latter characterized by a relapsing and remitting course with flares of high morbidity (reviewed in [2]). As initially described, the disease Correspondence: Dr. Hideki Ueno e-mail: hidekiu@baylorhealth.edu affects predominantly young women, with a female-to-male ratio of 9:1, albeit the reasons for this skewed sexual ratio remain poorly understood. The range of target organs is broad, and includes skin, joints, kidney, lung and the central nervous system. Lupus nephritis affects 40-70% of SLE patients with a various incidence dependent on ethnicity, age, group and gender, and constitutes a critical driver of morbidity and mortality (reviewed in [3]). In the 1950s, only 50% of patients with SLE survived 5 years; now, thanks to earlier diagnosis and better treatment, the majority of patients survive more than 10 years. Over time, infections and cardiovascular complications represent the leading causes of fatal outcomes (reviewed in [4]). A better understanding of human SLE pathogenesis is needed because few effective treatments are currently available, and only one drug has been approved for lupus in the past 50 years.Generation of autoantibodies is a hallmark of autoimmune diseases including SLE. Autoantibodies target a broad range of self-ant...

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Constitutively altered frequencies of circulating follicullar helper T cell counterparts and their subsets in rheumatoid arthritis

Cited by 80 publications

References 37 publications

Follicular helper T cells in rheumatoid arthritis

Follicular helper T cells in rheumatoid arthritis

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

T follicular helper (Tfh) cells in lupus: Activation and involvement in SLE pathogenesis

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