No abstract

Interleukin-37 (IL-37) possesses the function of down-regulate systemic and local inflammation. It is unknown whether IL-37 is expressed in human regulatory T cells (Tregs) and its role in modulating the immune response of Tregs. In the present study, cell surface molecules and secretory cytokines were analyzed in order to determine the function of IL-37 in regulating inhibitory effect of human CD4+CD25+Tregs. Meanwhile, the effects of IL-37 on T cell differentiation and proliferation as co-culture of CD4+CD25+Treg/CD4+CD25−T cell were also investigated. It was showed that IL-37 was expressed in cytoplasm of CD4+CD25+Tregs, and the levels of IL-37 were gradually elevated with the enhanced activity of CD4+CD25+Tregs. Secretory cytokines such as transforming growth factor (TGF)-β and interleukin (IL)-10, and expressions of cell surface molecules, including forkhead/winged helix transcription factor p3 (FOXP3) and cytotoxic T-lymphocyte associated antigen (CTLA)-4, were significantly decreased when IL-37 gene was silenced by siRNA. Furthermore, down-regulation of IL-37 expression in human CD4+CD25+Tregs obviously promoted proliferation of co-cultured T cell and differentiation, together with observably enhancement of IL-2 formation. These results demonstrated that IL-37 might manifest as a critical protein involving in immunosuppression of human CD4+CD25+Tregs.

Critical illnesses and injuries are recognized as major threats to human health, and they are usually accompanied by uncontrolled inflammation and dysfunction of immune response. The alpha 7 nicotinic acetylcholine receptor (α7nAchR), which is a primary receptor of cholinergic anti-inflammatory pathway (CAP), exhibits great benefits for critical ill conditions. It is composed of 5 identical α7 subunits that form a central pore with high permeability for calcium. This putative structure is closely associated with its functional states. Activated α7nAChR exhibits extensive anti-inflammatory and immune modulatory reactions, including lowered pro-inflammatory cytokines levels, decreased expressions of chemokines as well as adhesion molecules, and altered differentiation and activation of immune cells, which are important in maintaining immune homeostasis. Well understanding of the effects and mechanisms of α7nAChR will be of great value in exploring effective targets for treating critical diseases.

No abstract

Sestrin2 (SESN2) is a highly evolutionary conserved protein and involved in different cellular responses to various stresses. However, the potential function of SESN2 in immune system remains unclear. The present study was designed to test whether dendritic cells (DCs) could express SESN2, and investigate the underlying molecular mechanism as well as its potential significance. Herein, we firstly reported that SESN2 was expressed in DCs after high mobility group box-1 protein (HMGB1) stimulation and the apoptosis of DCs was obviously increased when SESN2 gene silenced by siRNA. Cells undergone SESN2-knockdown promoted endoplasmic reticulum (ER) stress (ERS)-related cell death, markedly exacerbated ER disruption as well as the formation of dilated and aggregated structures, and they significantly aggravated the extent of ERS response. Conversely, overexpressing SESN2 DCs markedly decreased apoptotic rates and attenuated HMGB1-induced ER morphology fragment together with inhibition of ERS-related protein translation. Furthermore, sesn2 −/− -deficient mice manifested increased DC apoptosis and aggravated ERS extent in septic model. These results indicate that SESN2 appears to be a potential regulator to inhibit apoptotic ERS signaling that exerts a protective effect on apoptosis of DCs in the setting of septic challenge.