Trends in Immunology最新文献

HIV-1 persists lifelong despite effective antiretroviral therapy, yet the mechanisms underlying this persistence remain incompletely understood. Recent work by Wei et al. and Gao et al. reveals that the transcription factor BACH2 orchestrates CD4⁺ T cell memory programs fostering long-term memory formation while limiting effector differentiation, thereby promoting HIV-1 persistence.

Mitochondrial lipid metabolism plays a pivotal role in tumor immunosurveillance and immune evasion. This review explores how mitochondrial regulation shapes immune cell metabolism within the tumor microenvironment (TME), focusing on the antitumor effects of the mitochondrial-fueled immune response and the detrimental impact of impaired mitochondrial function on immune cell cytotoxicity. Although current studies support this dual role, critical gaps remain, including how immune cells adapt differently to the lipid-rich TME, and how therapies can target lipid metabolism without harming immune memory. By synthesizing current findings and highlighting these uncertainties, this review highlights mitochondrial lipid metabolism as a promising therapeutic axis in cancer immunotherapy.

The interaction between the tumor immune microenvironment (TIME) and the tumor determines whether immune evasion or antitumor immunity prevails. Metabolic reprogramming is increasingly recognized as a critical factor shaping the tumor immune response. Glucose metabolism regulates the intrinsic cellular states of both immune and tumor cells, while simultaneously shaping the surrounding microenvironment. The glycolytic diversity of immune and tumor cells drives the complexity of the TIME. In this Review, we explore how glucose metabolism remodels the TIME and how these metabolic alterations influence immune effector function and immune evasion. We also highlight the potential for integrating microenvironmental modulation as a promising therapeutic strategy in glucose-targeted cancer therapies.

Programmed cell death (PCD) encompasses several tightly regulated molecular signalling pathways, leading to the controlled destruction of cells. Apoptosis is a non-immunogenic form of cell death that regulates homeostasis to cell stressors. In contrast, lytic forms of cell death - necroptosis, pyroptosis, and ferroptosis - promote inflammation, alerting the immune system to danger. As adaptive immune responders, T cells clonally expand in response to antigenic stimulation and rapidly contract following the clearance of infection. While the role of apoptosis in regulating these processes is relatively well understood, evidence for lytic death activity in T cells is emerging. This review provides an update on recent advances in the understanding of PCD pathways in conventional and unconventional T cells in diverse immune contexts.

The maintenance of serum antibodies requires the persistence of plasma cells within the bone marrow (BM). However, little is understood about why relatively few BM plasma cells live for extended periods. We consider two opposing viewpoints. We first consider the notion that sustained antibody titers requires localization of plasma cells to specialized BM niches where they access cell extrinsic survival factors, including extracellular ATP (eATP). We then consider the alternative possibility that plasma cell survival requires optimized cell intrinsic control of antibody synthesis supported by eATP stimulation of purinergic receptors. Based on the latter view we propose that many BM plasma cells fail to achieve maximal longevity due to suboptimal protein homeostasis rather than compromised access to cell extrinsic survival cues.

Inflammasomes have emerged as central regulators of (auto)immune pathology, including multiple sclerosis (MS). Once exclusively considered in the domain of myeloid cells, both canonical and noncanonical inflammasomes are now recognized in diverse immune and nonimmune populations relevant to MS, including T lymphocytes, blood-brain barrier (BBB) endothelial cells (EnC), and oligodendrocytes (ODCs). Elevated inflammasome activity is evident in patient-derived samples, particularly within active brain lesions. Experimental autoimmune encephalomyelitis (EAE) models confirm the pathogenic contribution of inflammasomes, as genetic deletion or pharmacological inhibition of inflammasomes mitigate disease. These advances position inflammasomes at the intersection of neuroinflammation and neurodegeneration, and highlight inflammasome inhibition as a promising therapeutic avenue currently under investigation in preclinical and early clinical studies.

Interleukin-27 (IL-27), a member of the IL-12 cytokine family, was long viewed primarily as a regulator of CD4⁺ T cell immunity. Subsequent studies revealed that IL-27 also directly modulates CD8⁺ T cells, displaying both stimulatory and inhibitory potential. Recent work extends this earlier literature, showing that IL-27 in infection and cancer can promote effector differentiation, sustain survival, and reverse dysfunction, often without the systemic toxicity associated with related cytokines. This review outlines the molecular features, signaling mechanisms, and cellular sources of IL-27, integrating emerging evidence from viral, tumor, and autoimmune settings. We propose that IL-27 operates not as an inherently pro- or anti-inflammatory cytokine but as a context-dependent tuner of CD8⁺ T cell cytotoxic immunity, offering new opportunities for therapeutic exploitation.

IL-22, produced by various cell types including T helper (Th) 17 cells and group 3 innate lymphoid cells (ILC3s), plays a pivotal role in gut homeostasis by acting on non-hematopoietic cells. It promotes epithelial barrier integrity, tissue repair, and antimicrobial defense. Beyond its established function in mucosal immunity, emerging evidence reveals IL-22's involvement in regulating intestinal metabolism and protecting against systemic metabolic dysregulation. This review highlights recent advances in preclinical mouse models and human clinical data in IL-22 biology, focusing on its dual role in immune defense and metabolic control. Given the strong link between inflammatory bowel disease (IBD) and metabolic disorders, we further discuss IL-22's therapeutic potential in mitigating both intestinal inflammation and related metabolic complications.

Chi and colleagues revealed that dietary cysteine enhances intestinal stem cell (ISC) regeneration, driving coenzyme A (CoA) synthesis and expansion of intraepithelial (IEL) CD8αβ⁺ T cells that secrete IL-22. This epithelial-immune crosstalk potentiates ISC repair after injury, highlighting a metabolism-immune axis linking cysteine sensing to tissue regeneration.

Recent research has shown that sequential colonization of the skin by various subsets of immune cells, particularly T cells, during perinatal stages forms layered surveillance networks crucial for maintaining skin tissue integrity and function. Here, we review our current understanding of key epigenetic and molecular mechanisms, along with maternal/external environmental factors, that regulate the sequential colonization of skin by different T cell subsets and their roles in establishing and maintaining skin tissue homeostasis. We propose that establishment of a skin-resident T cell system is developmentally programmed in coordination with maturation of skin structural barriers to adapt to environmental changes during perinatal stages, while dysregulation during this critical 'window of opportunity' could have lifelong impacts on the health of both the skin and body.