Cellular metabolism regulates the differentiation and function of T-cell subsets

Tcells are an important component of adaptive immunity and protect the host from infectious diseases and cancers.However,uncontrolled T cell immunity may cause autoimmune disorders.In both situations,antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens.Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion.Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets.The realm of immunometabolism research is undergoing swift advancements.Encapsulating all the recent progress within this concise review in not possible.Instead,our objective is to provide a succinct introduction to this swiftly progressing research,concentrating on the metabolic intricacies of three pivotal nutrient classes—lipids,glucose,and amino acids—in T cells.We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells.Moreover,we delve into the prospect of“editing”metabolic pathways within T cells using pharmacological or genetic approaches,with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.

GPR34 senses demyelination to promote neuroinflammation and pathologies

Sterile neuroinflammation is a major driver of multiple neurological diseases.Myelin debris can act as an inflammatory stimulus to promote inflammation and pathologies,but the mechanism is poorly understood.Here,we showed that lysophosphatidylserine(LysoPS)-GPR34 axis played a critical role in microglia-mediated myelin debris sensing and the subsequent neuroinflammation.Myelin debris-induced microglia activation and proinflammatory cytokine expression relied on its lipid component LysoPS.Both myelin debris and LysoPS promoted microglia activation and the production of proinflammatory cytokines via GPR34 and its downstream PI3K-AKT and ERK signaling.In vivo,reducing the content of LysoPS in myelin or inhibition of GPR34 with genetic or pharmacological approaches reduced neuroinflammation and pathologies in the mouse models of multiple sclerosis and stroke.Thus,our results identify GPR34 as a key receptor to sense demyelination and CNS damage and promote neuroinflammation,and suggest it as a potential therapeutic target for demyelination-associated diseases.