As a Traditional Chinese Medicine, Paeonia lactiflora Pallas has been used to treat pain, inflammation and immune disorders for more than 1000 years in China. Total glycoside of paeony (TGP) is extracted from the dried root of Paeonia lactiflora Pallas. Paeoniflorin (Pae) is the major active component of TGP. Our research group has done a lot of work in the pharmacological mechanisms of Pae and found that Pae possessed extensive anti-inflammatory and immune regulatory effects. Pae could inhibit inflammation in the animal models of autoimmune diseases, such as experimental arthritis, psoriatic mice and experimental autoimmune encephalomyelitis, and so on. Pae modulates the functions and activation of immune cells, decreases inflammatory medium production, and restores abnormal signal pathway. Pae could balance the subsets of immune cells through inhibiting abnormal activated cell subsets and restoring regulatory cell subsets. Pae could regulate signaling pathways (GPCR pathway, MAPKs /NF-κB patway, PI3K /Akt /mTOR pathway, JAK2 /STAT3 pathway, TGFβ /Smads, and etc.). TGP is composed of Pae, hydroxyl-paeoniflorin, paeonin, albiflorin and benzoylpaeoniflorin etc. Pae accounts for more than 40% of TGP. Like Pae, TGP has anti-inflammatory and immune regulatory effects. TGP has been widely used to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, allergic contact dermatitis, and etc. in China. Furthermore, TGP has some superior features with immune regulation, gentle effect, many indications and few adverse drug reactions. These findings suggest that TGP may be a promising anti-inflammatory and immune drug with soft regulation and has more superiority in the treatment of AIDs. Currently, TGP is used for the treatment of RA, SLE and other AIDs in more than 1000 hospitals in China, which obtained great social and economic benefits.

Chimeric antigen receptor (CAR)-T cell therapy has been shown to be an effective treatment for hematological tumors, but the treatment of solid tumors still lacks effectiveness. In the tumor microenvironment, macrophages are the innate immune cells with the highest infiltration rate. Tumor-associated macrophages (TAMs) stimulate angiogenesis, increase tumor invasion, and mediate immunosuppression. Because macrophages can infiltrate solid tumor tissue and interact with almost all cellular components in the tumor microenvironment (including tumor cells, immune cells such as T-cells, NK cells, DCs, and other resident non-immune cells), researchers are trying to use macrophages modified with CAR (CAR-M) against solid tumors. This review describes recent reports of CAR-M-based tumor treatments and summarizes their shortcomings and future applications.

The interaction between T cell and dendritic cells (DCs) that leads to T cell activation affects the progression of the immune response including autoimmune diseases. Antigen presentation on immune cell surface, formation of an immunological synapse (IS), and specific identification of complex by T cells including two activating signals are necessary steps that lead to T cell activation. The formation of stimulatory IS involves the inclusion of costimulatory molecules, such as ICAM-1/LFA-1 and CD28/B7-1, and so on. Some fusion proteins and monoclonal antibodies targeting costimulatory molecules have been developed and approved to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), type I diabetes (T1D), inflammatory bowel disease (IBD), and psoriasis. These biological agents, including CTLA-4- and LFA-3-Ig, anti-CD3 monoclonal antibody, could prevent the successful engagement of DCs by T cell with significant efficacy and safety profile. In this article, we reviewed the molecular mechanisms of T cell activation during the interaction between T cells and DCs, and summarized some biological agents that target costimulatory molecules involved in the regulation of T cell activation.

Macrophages maintain a dynamic balance in physiology. Various known or unknown microenvironmental signals influence the polarization, activation and death of macrophages, which creates an imbalance that leads to disease. Rheumatoid arthritis (RA) is characterized by the massive infiltration of a variety of chronic inflammatory cells in synovia. Abundant activated macrophages found in RA synovia are an early hallmark of RA, and the number of these macrophages can be decreased after effective treatment. In RA, the proportion of M1 (pro‐inflammatory macrophages) is higher than that of M2 (anti‐inflammatory macrophages). The increased pro‐inflammatory ability of macrophages is related to their excessive activation and proliferation as well as an enhanced anti‐apoptosis ability. At present, there are no clinical therapies specific to macrophages in RA. Understanding the mechanisms and functional consequences of the heterogeneity of macrophages will aid in confirming their potential role in inflammation development. This review will outline RA‐related macrophage properties (focus on polarization, metabolism and apoptosis) as well as the origin of macrophages. The molecular mechanisms that drive macrophage properties also be elucidated to identify novel therapeutic targets for RA and other autoimmune disease.

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.