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The serine proteases of Mycobacteria tuberculosis (Mtb) are important contributors to the process of bacterial invasion and its pathogenesis. In the present study, we systematically characterized the role of the Rv1043c protein in Mycobacterium infection by purifying the Rv1043c protein in Escherichia coli and constructing a Mycobacterium smegmatis (Msg) strain overexpressing Rv1043c (Msg_Rv1043c). We found that Rv1043c had serine protease activity and localized to the surface of Mtb. We determined that the optimal pH and temperature for the Rv1043c serine protease were 9.0 and 45°C, respectively. Moreover, the serine protease activity of Rv1043c was enhanced by divalent metal ions of Ca2+ and Mg2+. Site-directed mutagenesis studies demonstrated that the serine 279 residue in Rv1043c plays a catalytic role. Additionally, mouse model studies confirmed that Rv1043c significantly enhanced the survival of Msg in vivo, induced pulmonary injury and lung cell apoptosis, and promoted the release of pro-inflammatory cytokines interleukin-1β and interleukin-6 in mice. This study presents novel insights into the relationship between mycobacterial serine protease and the pathogenesis of the disease.

Abstract Systemic lupus erythematosus (SLE) is a chronic rheumatic disorder. Endothelin-1, a vasoconstrictor, belongs to the endothelin family and is associated with vascular-related damages. To date, association between ET-1 and pathogenesis of SLE remains unclear. This case–control study was carried out by 314 SLE, 252 non-SLE diseases patients and 500 healthy controls. Serum ET-1, CCN3, IL-28B levels were detected by ELISA, and ET-1 gene polymorphisms (rs5369, rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs4145451, rs6458155, rs9369217) were genotyped with Kompetitive Allele-Specific PCR. SLE patients had high levels of ET-1, which were correlated with some clinical, laboratory features. Serum CCN3, IL-28B levels were higher in SLE patients, and ET-1 levels were positively correlated with the two cytokines. Rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs6458155 and rs2070699 were associated with SLE risk. Rs2070699 (T, TT) was related to SLE patients with alopecia. Rs5370 (T, TT, TG), rs1476046 (G,GA), rs2071942 (G,GA) and rs2071943 (G,GA) were associated with SLE patients with pericarditis, pyuria and fever manifestation, respectively. Rs3087459 (CC) and rs9369217 (TC) were related to SLE patients with positive anti-SSB antibody. Rs5369 (AA) was associated with IgG and CRP levels in SLE patients. In conclusion, elevated serum ET-1 in SLE patients may be a potential disease marker, and its gene polymorphisms were related to SLE susceptibility.

Systemic lupus erythematosus (SLE) is an inflammatory disorder related to immunity dysfunction. The Th1 cell family including Th1 cells, transcription factor T-bet, and related cytokines IFNγ, TNFα, IL-2, IL-18, TGF-β, and IL-12 have been widely discussed in autoimmunity, such as SLE. In this review, we will comprehensively discuss the expression profile of the Th1 cell family in both SLE patients and animal models and clarify how the family members are involved in lupus development. Interestingly, T-bet-related age-associated B cells (ABCs) and low-dose IL-2 treatment in lupus were emergently discussed as well. Collection of the evidence will better understand the roles of the Th1 cell family in lupus pathogenesis, especially targeting IL-2 in lupus.

Hypoxia-inducible factor-1α (HIF-1α) is a primary metabolic sensor, and is expressed in different immune cells, such as macrophage, dendritic cell, neutrophil, T cell, and non-immune cells, for instance, synovial fibroblast, and islet β cell. HIF-1α signaling regulates cellular metabolism, triggering the release of inflammatory cytokines and inflammatory cells proliferation. It is known that microenvironment hypoxia, vascular proliferation, and impaired immunological balance are present in autoimmune diseases. To date, HIF-1α is recognized to be overexpressed in several inflammatory autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and function of HIF-1α is dysregulated in these diseases. In this review, we narrate the signaling pathway of HIF-1α and the possible immunopathological roles of HIF-1α in autoimmune diseases. The collected information will provide a theoretical basis for the familiarization and development of new clinical trials and treatment based on HIF-1α and inflammatory autoimmune disorders in the future.

Intestinal stem cells are an important part of maintaining the stability of intestinal barrier function, which is closely related to intestinal homeostasis, intestinal epithelial renewal, and repair of intestinal damage. Normal physiological activities of the human body cannot be separated from energy intake and metabolism, and the differentiation fate of stem cells is affected by energy metabolism, and impaired intestinal barrier is associated with the development of many intestinal diseases. Therefore, this paper focuses on intestinal stem cells, takes energy metabolism and metabolites as the background to investigate how energy metabolism and metabolites regulate the function and activity of stem cells, thus regulating the function of intestinal barrier and providing ideas for the treatment of various intestinal diseases; in addition, with the in-depth research of modern medical science in protecting intestinal barrier, the theory of traditional Chinese medicine (TCM) that cares for spleen and stomach is gradually showing its scientific validity, with the hope of providing ideas for the subsequent research.