Yaxiong Deng

T cell metabolism constitutes a pivotal regulator of cellular states and disease progression. At the cellular level, the metabolic status of T cells directly governs their function and fate determination. Senescent T cells, for instance, exhibit fundamentally distinct metabolic signatures compared to effector T subsets, underscoring metabolic reprogramming as a critical mechanistic driver of T cell senescence. In pathological contexts, aberrant metabolic rewiring in T cells disrupts differentiation, function, and cellular survival, thereby contributing to disease onset and progression. Notably, the pathological accumulation of senescent T cells observed across chronic inflammatory and autoimmune diseases positions metabolism-driven T cell senescence as a key nexus linking metabolic dysregulation to clinical manifestations. Consequently, targeted modulation of T cell metabolism offers a dual therapeutic potential: direct intervention in cellular states (e.g., delaying senescent phenotypes) and synergistic amelioration of disease pathology through functional immune restoration. This Review summarizes the fundamental principles of T cell metabolic reprogramming, its causative role in propelling T cell senescence, and the dynamic interplay between metabolic dysfunction, T cell senescence, and disease pathogenesis. We specifically dissect these relationships in two immunologically divergent conditions—systemic lupus erythematosus (SLE, exemplifying hyperactive autoimmunity) and chronic infection (Chronic HIV infection, reflecting immune exhaustion)—to establish a mechanistic framework for developing metabolism-targeted immunotherapeutics that precisely restore T cell efficacy.

Background: Interleukin-17 (IL-17) monoclonal antibody drugs have been increasingly significant in the treatment of psoriasis, but it is not clear whether the efficacy is equivalent across ethnicities.Objective: To explore the differences of short-term efficacy of IL-17 inhibitors between Caucasians and Asians.Methods: The pooled log risk ratio (logRR) between the groups was estimated. The meta-regression analysis on the logRR was performed, with the proportion of Caucasian patients as the covariate. The subgroup analysis was performed by specific IL-17 inhibitors.Results: Of the 1,569 potentially relevant studies, sixteen randomized controlled trials (RCTs) were included. For the Psoriasis Area and Severity Index 75 (PASI 75) response at week 12, the pooled logRR of the Asian group and the Caucasian group was 2.81 (95% CI: 2.27–3.35, p < 0.001) and 2.93 (95% CI: 2.71–3.16, p < 0.001), respectively, indicating no significant difference of efficacy between Asians and Caucasians. The meta-regression analysis did not show an association of the proportion of Caucasians with the effect size (β = 0.3203, p = 0.334). In the subgroup analysis, the comparison results of secukinumab were consistent with the main analysis.Limitations: Only the short-term efficacy was explored. The data from Asian countries were limited.Conclusions: The short-term efficacy of IL-17 inhibitors in the treatment of psoriasis has no significant difference between Caucasians and Asians.Systematic Review Registration: PROSPERO, identifier CRD42020201994, https://www.crd.york.ac.uk/prospero/.