No abstract

Chen et al. show that regulatory T cells adhere to dendritic cells (DCs) with high binding forces. This strong binding causes cytoskeletal polarization in the latter, which limits DCs’s ability to form productive engagement with other antigen-specific T cells.

SUMMARYThe NLRP3 inflammasome senses a range of cellular disturbances, although no consensus exists regarding a common mechanism. Canonical NLRP3 activation is blocked by high extracellular K+, regardless of the activating signal. We report here that canonical NLRP3 activation leads to Ca2+ flux and increased calpain activity. Activated calpain releases a pool of Caspase-1 sequestered by the cytoskeleton to regulate NLRP3 activation. Using electrophysiological recording, we found that resting-state eukaryotic membrane potential (MP) is required for this calpain activity, and depolarization by high extracellular K+ or artificial hyperpolarization results in the inhibition of calpain. Therefore, the MP/Ca2+/calpain/ Caspase-1 axis acts as an independent regulatory mechanism for NLRP3 activity. This finding provides mechanistic insight into high K+-mediated inhibition of NLRP3 activation, and it offers an alternative model of NLRP3 inflammasome activation that does not involve K+ efflux.

The suppression mechanism of regulatory T cells is an intensely investigated topic. As our focus has shifted towards a model centered on indirect inhibition of dendritic cells, a universally applicable effector mechanism controlled by FoxP3 expression has not been found. Here, we report that FoxP3 blocks the transcription of ER Ca2+-release channel ryanodine receptor 2. Reduced RyR2 shuts down basal Ca2+ oscillation in Tregs, which reduces m-Calpain activities that is needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency renders the CD4+ T cell pool to become immune suppressive, and behave in the same manner as FoxP3+ Tregs in viral infection, asthma, hypersensitivity, colitis and tumor development. In the absence of FoxP3, RyR2-deficient CD4+ T cells rescue the systemic autoimmunity associated with Scurfy mice. Therefore, FoxP3-mediated Ca2+ signaling inhibition may be a central effector mechanism of Treg immune suppression.

With the continuous development and expansion of the water reclamation and reuse market, it is vital to ensure water quality safety and stability over the entire water reuse system. Because the quality of reclaimed water is distinct from that of drinking water, it is likely to deteriorate, even after advanced treatment, during distribution and transport. This review identifies the common microbial corrosion in reclaimed water distribution pipelines and end use applications (e.g. industrial cooling system) and the dominant corrosive microorganisms in reclaimed water. The microbial corrosion mechanism and the affecting factors on microbial corrosion are discussed in depth. Moreover, this study also proposes possible strategies for dealing with pipeline microbial corrosion, including the control of the assimilable organic carbon content via coagulation and filtration processes as well as disinfection technologies for microbial inactivation. This study is of great novelty to provide a comprehensive overview of microbial corrosion in reclaimed water distribution and application and point out future directions towards sustainable and long-lasting water reuse.