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Abstract As antigen-presenting cells (APC), B cells exert a variety of immune regulatory functions mainly by presenting antigens, triggering immune response, and producing antibodies for immune regulation. Regulatory B cells (Bregs) are special subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Bregs suppress immune response through inhibiting the differentiation of dendritic cells (DCs), suppressing the proliferation of helper T1(TH1) cells and helper T17 (TH17) cells, inducing the differentiation of fork head transcription factor p3 positive regulatory T cells (FoxP3+ Tregs). Different subsets of Bregs have distinct phenotypes and markers. Different subsets of Bregs participate in immune modulation by different ways. The absence or loss of Bregs exacerbates the severity of many disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and graft-versus-host-disease (GVHD). Bregs are also involved in tumor immunosuppressive effect and inhibit the antitumor immune process. In this article, we review the research advances of Bregs in autoimmune diseases, GVHD and tumor. Highlights • Previous studies have shown that regulatory B cells play important roles in inflammatory diseases and tumor. • There is no systematic review of the role of regulatory B cells in inflammatory diseases and tumor. • In this paper, the role of regulatory B cells in inflammatory diseases and tumors is systematically reviewed. • This article provides researchers with the latest systematic research of regulatory B cells. [ABSTRACT FROM AUTHOR]

• Rapid metabolism and some allergic reactions greatly limit the clinical application of SIN. • Compensating for its limitations and reducing side effects may enable sin to be better applied in the clinic. • SIN has great therapeutic potential in treating autoimmune diseases. • SIN in combination with DMARDs has great potential. Autoimmune diseases (ADs), with significant effects on morbidity and mortality, are a broad spectrum of disorders featured by body's immune responses being directed against its own tissues, resulting in chronic inflammation and tissue damage. Sinomenine (SIN) is an alkaloid isolated from the root and stem of Sinomenium acutum which is mainly used to treat pain, inflammation and immune disorders for centuries in China. Its potential anti-inflammatory role for treating immune-related disorders in experimental animal models and in some clinical applications have been reported widely, suggesting an inspiring application prospect of SIN. In this review, the pharmacokinetics, drug delivery systems, pharmacological mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of SIN, and the possibility of SIN as adjuvant to disease-modifying anti-rheumatic drugs (DMARDs) therapy were summarized and evaluated. This paper aims to reveal the potential prospects and limitations of SIN in the treatment of inflammatory and immune diseases, and to provide ideas for compensating its limitations and reducing the side effects, and thus to make SIN better translate to the clinic. [ABSTRACT FROM AUTHOR]

Abstract: Icaritin is a native compound from Epimedium Genus, a traditional Chinese herbal medicine which is effective in treating asthma, autoimmune diseases and viral infections. In the present paper, the immunosuppressive effects of icaritin were found through in vitro and in vivo studies. Icaritin could dose-dependently inhibit murine CD4+ T cells proliferation stimulated with mitogens or specific antigen ovabumin (OVA). Icaritin at 0.25–25μM could down-regulate T cell activation marker CD25 expression and inhibit IL-2 production. It could also reduce the Th1 cytokine IFN-γ production significantly if the T cells were activated by ConA or anti-CD3; while the inhibition of IL-4 secretion was only seen on anti-CD3 activated T cells treated with low concentrations of icaritin. In vivo study showed that treatment of icaritin at 10mg/kg/day on mice could suppress the immune response with prolonged allograft skin survival. Further study demonstrated that it reduced the alloantigen-induced splenocytes proliferation and Th1/Th2 cytokines. It could also increase NF-AT luciferase activity in Jurkat-NF-AT-luc T cells. The above results suggested that icaritin might be used to treat Th1 dominated immune diseases by interfering T cells activation with mechanism different to CsA. [Copyright &y& Elsevier]

Type 1, or cellular, immune response is characterized by overproduction of TNF-α, IFN-gamma, IL-1, IL-2 and IL-8 and is the underlying immune mechanism of psoriasis, alopecia areata, rheumatoid arthritis, Crohn''s disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis (EAU). Type 2 immune response is seen in antibody-mediated autoimmune diseases. Based on the pharmacokinetic effects of cetirizine and allopurinol, this paper introduces these two safe and inexpensive drugs as novel potential agents against cell-mediated autoimmune disorders.Cetirizine, supposed to inhibit DNA binding activity of NF-kappa B, inhibits the expression of adhesion molecules on immunocytes and endothelial cells and the production of IL-8 and LTB4, two potent chemoattractants, by immune cells. It induces the release of PGE2, a suppressor of antigen presentation and MHC class II expression, from monocyte/macrophages and reduces the number of tryptase positive mast cells in inflammation sites. Tryptase is a chemoattractant, generates kinins from kininogen, activates mast cells, triggers maturation of dendritic cells and stimulates the release of IL-8 from endothelial cells and the production of Th1 lymphokines by mononuclear immunocytes.Allopurinol is a free radical scavenger, suppresses the production of TNF-α and downregulates the expression of ICAM-1 and P2X7 receptors on monocyte/macrophages. ICAM-1 serves as a ligand for LFA-1 (on T lymphocytes), allowing proper antigen presentation. P2X7 receptors are thought to be involved in IL-1β release, mitogenic stimulation of T lymphocytes and the probable cytoplasmic communication between macrophages and lymphocytes at inflammation sites.Allopurinol was markedly more effective than prednisolone in treating experimental autoimmune uveitis and in combination with cyclosporine suppressed the inflammatory reaction of this condition more effectively than either agent alone.As allopurinol is a competitive inhibitor of xanthine oxidase and decreases serum levels of uric acid, which is protective against multiple sclerosis, it should preferably be coadministered with uric acid precursors in the treatment of this condition.Cetirizine and allopurinol may prove of benefit in the treatment of various cellular autoimmune disorders. [Copyright &y& Elsevier]

• Two factors of Bregs are related to AITD development. • Peripheral blood Bregs decreased with dysfunction. • Bregs compensatory increases due to the dysfunction. • It can be suggested that may have an automatic feedback regulation mechanism. • Bregs promoteTh2 cell differentiation and its function decreased by IL-4. • Bregs can inhibit the Th1. It is possible that the high Th1 response of HT and TAO patients may increase the frequency of Bregs. Regulatory B cells (Bregs) are a subset of B cells that can downregulate the immune and inflammatory responses. The development of B cells in humans and mice is differs. The Positioning and targeted regulation of Bregs has a positive effect on autoimmune diseases. Autoimmune thyroid disease (AITD) is a common autoimmune disease. This review introduces the history and origins of Bregs. It summarizes the different phenotypes and functionalities of Breg cells related to AITD and analyzes the reasons for the differences in Breg expression frequencies in Graves disease (GD) and Hashimoto's Thyroiditis (HT). A number of functional defects of regulatory B cells may be the newly discovered cause of AITD. This paper sheds new light on the role and prospects of Bregs in the progression and treatment of AITD. [ABSTRACT FROM AUTHOR]

• IL-2 immunotherapeutic agent in the treatment of autoimmune diseases. • The structural changes benefit its specificity interaction with specific receptors. • Previous review give us support for the submission of future experimental papers. Interleukins, also called cytokines are secretory proteins that bind to specific receptors and play a critical role in the intercellular communication between cells of the immune system. Cytokines are mainly produced by T lymphocytes, macrophages and eosinophils. Among its functions are the activation and suppression of immune system responses, induction of cell division and regulation of memory cells. Interleukin 2 (IL-2) is a secretory monomeric glycoprotein composed of 149 amino acids containing a signal peptide of 20 amino acids. It is classified as a member of the type I cytokines family. IL-2 binds to its receptor (IL-2R receptor) with high affinity and its signaling function promotes the activation of various subtypes of lymphocytes during the process of cell differentiation to generate an immune or homeostatic response. The specificity of IL-2 depends on its binding to low, medium or high-affinity receptors. Interleukin 2 acts as a regulator of the proliferation of CD4+ and CD8+ T cells. There is a relationship between IL-2 and autoimmune diseases due to its influence in the differentiation of T helper cells, which in turn directly influence immunological response processes. Therefore, IL-2 is a key element in the control and treatment of those diseases. In recent years, many therapeutic agents based on biomolecules and recombinant chimeric proteins have been developed to treat different autoimmune diseases. In this review, we focus on the use of interleukin 2 as a versatile therapeutic agent, alone or associated with other molecules to increase the efficiency of autoimmune disease treatment. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 (DPP-4) is a serine protease, which has enzymatic activity to selectively clean the N-terminal dipeptide of peptides and proteins with proline or alanine in the second position. DPP-4 inhibitor has been widely used for the treatment of type 2 diabetes by increasing the level of the glucagon-like peptide-1 and decreasing the glucose level. DPP-4, also known as lymphocyte cell surface protein CD26, plays a core role of T cell immunity. Many roles of CD26 in other immune cells have been found. As a "moonlight protein", the effect of CD26 in autoimmune diseases has attracted more and more attention. The paper reviewed the function and potential effect of CD26 in autoimmune diseases, which shows CD26 may be a new target of autoimmune diseases deserved further study. Unlabelled Image • DPP-4, also known as CD26, plays a core role of T cell immunity • As a "moonlight protein", the effect of CD26 in autoimmune diseases has attracted more and more attention. • We reviewed the function and potential effect of CD26 and DPP-4 inhibitors in autoimmune diseases. • CD26 might be a new target of autoimmune diseases deserved further study. [ABSTRACT FROM AUTHOR]