Follicular helper T cells: potential therapeutic targets in rheumatoid arthritis

Lü, Jian; Wu, Jing; Xia, Xueli; Peng, Huiyong; Wang, Shengjun

doi:10.1007/s00018-021-03839-1

Cited by 31 publications

(17 citation statements)

References 119 publications

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“…IL-12 can lead to Th1 and Tfh1 cell differentiation by regulating T-bet and Bcl-6 signals to secrete IFN-g and enhance antibody isotype class-switching (19,33). The differentiation of Tfh2 cells is dependent on IL-4, which is also self-secreted by Tfh2 cells and can contribute to humoral immune responses, and IL-17 from Tfh17 cells can also promote antibody production and classswitching (19,(38)(39)(40). These results indicate that SLE is a complex autoimmune disease characterized by dysfunction of cTfh cell subsets and disorder of Tfh-associated cytokines.…”

Section: Discussionmentioning

confidence: 94%

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

Jin

Chen²,

Wu³

et al. 2022

Front. Immunol.

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ObjectiveSystemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by multiple autoantibodies, resulting in multiple organ and tissue damages. These pathogenic autoantibodies produced by B cells are closely correlated with follicular helper T (Tfh) cell subsets that play a fundamental role in the pathogenesis of SLE. The aim of the present study was to study the phenotype and role of circulating Tfh (cTfh) cell subsets and associated B cell subpopulations in active and inactive SLE patients.MethodsThirty SLE outpatients and 24 healthy controls (HCs) were enrolled in this study. The frequency of cTfh cell and B cell subsets in peripheral blood mononuclear cells (PBMCs) and the plasma levels of eight cytokines were determined by flow cytometry, and plasma IL-21 levels were measured by ELISA. Meanwhile, we used MRL/lpr mice as the model of SLE to research the alterations of Tfh cells in the thymus and spleen of mice.ResultsFrequencies of CD4+CXCR5+CD45RA-effector cTfh cells, PD1+cTfh, PD1+ICOS+cTfh, PD1+cTfh1, PD1+cTfh2, PD1+cTfh17, and PD1+ICOS+cTfh1 cells as well as plasmablasts showed significant differences among HC, active and inactive SLE patients. Moreover, cytokines typically associated with cTfh cells, including IL-6 and IL-21, were elevated in active SLE patients compared to inactive SLE patients and HCs. Additionally, a positive correlation was observed between PD1+ICOS+ cTfh or PD1+ICOS+ cTfh1 cell frequencies and plasmablasts or IL-21 levels, as well as between plasmablasts. We also found PD1+ICOS+ Tfh cells expansion in both thymus and spleen of MRL/lpr mice, accompanied by increased frequencies in B cells and plasmablasts, meanwhile, cTfh1which expressing IFN-γ was increased in the peripheral blood of MRL/lpr mice.ConclusionTfh cell subsets and plasmablasts may play a fundamental role in the pathogenesis of SLE and may provide potential targets for therapeutic interventions for SLE.

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Section: Discussionmentioning

confidence: 94%

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

Jin

Chen²,

Wu³

et al. 2022

Front. Immunol.

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“… 138 , 139 IL-21 affects local T cell activation and proliferation but also promotes aggressive migration, invasion, and metalloproteinase secretion by FLSs. 140 , 141 Neutralization of IL-21 and IL-15 inhibits their proinflammatory cytokine production in RA synovial cell culture. 142 In addition, high levels of serum soluble protein were detected in patients with RA.…”

Section: T Helper Cells Are Involved In the Immunomodulatory Process ...mentioning

confidence: 99%

Immunomodulatory role of T helper cells in rheumatoid arthritis

Luo

Wang

et al. 2022

Bone & Joint Research

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Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps. Cite this article: Bone Joint Res 2022;11(7):426–438.

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“…Special components in synovial tissue and endogenous substances produced in vivo can also be presented by dendritic cells as self-antigens, activate CD4+ T cells and lead to inflammation [ 18 ]. T cells follicular helper (Tfh) is a subtype of CD4+ T cells, which can help B cells and regulate the production of antibodies, so as to further participate in the occurrence of RA [ 19 ]. In addition, inducing anti-inflammatory M2 macrophages, inhibiting the production of inflammatory factors and alleviating synovitis of RA are also the focus of current research.…”

Section: Discussionmentioning

confidence: 99%

Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis

Wang

Xue

Zhou³

2022

J Transl Med

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Background Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are chronic autoimmune diseases, but they are usually difficult to distinguish in the early stage of the diseases. The purpose of this study is to explore the differences of immune mechanism and diagnostic markers through bioinformatics analysis. Methods First, microarray datasets from patients with SpA, RA and normal controls were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between groups were identified in R software. Functional and pathway enrichment of DEGs were analyzed by David database. Then, we screened the hub genes using Cytoscape plugin, and constructed the protein–protein interaction (PPI) network and heatmap of hub genes. After that, CIBERSORT was used to evaluate the differences and connections of immune cells in SpA and RA, and screened out diagnostic markers. Correlation analysis was used to analyze the relationship between immune cells and diagnostic markers. Finally, quantitative real-time polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of immunodiagnostic markers. Results We obtained three datasets, from which we can see that the functional enrichment of DEGs is mainly in cell chemotaxis, lymphocyte activation, primary immunodeficiency and other immune responses. The difference of immune cells between SpA, RA and normal control was concentrated in B, T lymphocytes cells, macrophages and dendritic cells. C19orf12 + S1PR3 is most associated with these immune cells and S1PR3 can be used as a diagnostic marker of this kind of immune diseases. In addition, MZB1 + XIST is closely related to T cells, NK cells and dendritic cells, and is expected to be used as a marker to distinguish the two diseases. Conclusion Although the clinical manifestations of SpA and RA are similar, the pathogenesis is different. The screening of immune cells and diagnostic markers provides a more accurate target for the treatment of this kind of diseases.

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Follicular helper T cells: potential therapeutic targets in rheumatoid arthritis

Cited by 31 publications

References 119 publications

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus

Immunomodulatory role of T helper cells in rheumatoid arthritis

Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis

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