Balance of Tfh/Tfr cell is critically important for the maintenance of immune tolerance, as evidenced by the fact that T follicular helper (Tfh) cells are central to the autoantibodies generation through providing necessary help for germinal center (GC) B cells, whereas T follicular regulatory (Tfr) cells significantly inhibit autoimmune inflammation process through restraining Tfh cell responses. However, signals underlying the regulation of Tfh and Tfr cells are largely undefined. Regulatory B cells (Bregs) is a heterogeneous subpopulation of B cells with immunosuppressive function. Considerable advances have been made in their functions to produce anti‐inflammatory cytokines and to regulate Th17, Th1, and Treg cells in autoimmune diseases. The recent identification of their correlations with dysregulated Tfr/Tfh cells and autoantibody production makes Bregs an important checkpoint in GC response. Bregs exert profound impacts on the differentiation, function, and distribution of Tfh and Tfr cells in the immune microenvironment. Thus, unraveling mechanistic information on Tfh-Breg and Tfr-Breg interactions will inspire novel implications for the establishment of homeostasis and prevention of autoantibodies in diverse diseases. This review summarizes the dysregulation of Tfh/Tfr cells in autoimmune diseases with a focus on the emerging role of Bregs in regulating the balance between Tfh and Tfr cells. The previously unsuspected crosstalk between Bregs and Tfh/Tfr cells will be beneficial to understand the cellular mechanisms of autoantibody production and evoke a revolution in immunotherapy for autoimmune diseases.
Single-cell RNA sequencing (scRNA-seq) technology can analyze the transcriptome expression level of cells with high-throughput from the single cell level, fully show the heterogeneity of cells, and provide a new way for the study of multicellular biological heterogeneity. Synovitis is the pathological basis of rheumatoid arthritis (RA). Synovial fibroblasts (SFs) and synovial macrophages are the core target cells of RA, which results in the destruction of articular cartilage, as well as bone. Recent scRNA-seq technology has made breakthroughs in the differentiation and development of two types of synovial cells, identification of subsets, functional analysis, and new therapeutic targets, which will bring remarkable changes in RA treatment.
Purpose
Low-dose interleukin-2 (ld-IL-2) has been shown to regulate the balance between effector T and regulatory T (Treg) cells and has been used in several clinical trials to treat autoimmune diseases including rheumatoid arthritis (RA). In this study, we investigated the effects of ld-IL-2 on collagen-induced arthritis (CIA) in mice.
Methods
Arthritis severity in CIA mice was measured using the arthritis index (AI), radiographs, and hematoxylin and eosin staining. Cytokines were detected using enzyme-linked immunosorbent assay. Gut microbiota alterations and short-chain fatty acid production were analyzed through 16S rRNA sequencing and gas chromatography.
Results
The AI scores of CIA mice treated with ld-IL-2 were significantly lower compared to the model group, which significantly reduced the severity of arthritis. Ld-IL-2 also altered the gut microbiota in CIA mice. The diversity, composition, and dominant species of gut microbiota were altered by ld-IL-2 treatment. Ld-IL-2 also increased short-chain fatty acid levels. There was a strong correlation between ld-IL-2 treatment and improved gut microbiota.
Conclusion
Ld-IL-2 significantly ameliorated joint inflammation and bone damage and improved gut microbial dysbiosis in CIA, indicating that it may be a promising therapy for RA patients.
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