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.
Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive arthritis as the main manifestation and synovitis as the basic pathological change, which can cause progressive destruction of articular cartilage and bone, ultimately leading to joint deformity and loss of function. Since its introduction in the 1980s and its widespread use in the treatment of RA, low-dose methotrexate (MTX) therapy has dramatically changed the course and outcome of RA treatment. The clinical use of this drug will be more rational with a better understanding of the pharmacology, anti-inflammatory mechanisms of action and adverse reaction about it. At present, the current clinical status of newly diagnosed RA is that MTX is initiated first regardless of the patients’ suitability. But up to 50% of patients could not reach adequate clinical efficacy or have severe adverse events. Prior to drug initiation, a prognostic tool for treatment response is lacking, which is thought to be the most important cause of the situation. A growing body of studies have shown that differences in microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) in the gastrointestinal tract of RA patients may at least partially determine their bioavailability and/or subsequent response to MTX. Based on this, some researchers established a random forest model to predict whether different RA patients (with different gut microbiome) would respond to MTX. Of course, MTX, in turn, alters the gut microbiome in a dose-dependent manner. The interaction between drugs and microorganisms is called pharmacomicrobiology. Then, the concept of precision medicine has been raised. In this view, we summarize the characteristics and anti-inflammatory mechanisms of MTX and highlight the interaction between gut microbiome and MTX aiming to find the optimal treatment for patients according to individual differences and discuss the application and prospect of precision medicine.
Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus‐expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus‐expressing mice were gavaged daily with phosphate‐buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.
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