Immunometabolism (Cobham (Surrey, England))最新文献

The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of hematological cancers has marked a new era in cancer care, with seven products being FDA approved since 2017. However, challenges remain, and while profound effects are observed initially in myeloma, the majority of patients relapse, which is concomitant with poor CAR T cell persistence. Similarly, the efficacy of CAR T cell therapy is limited in solid tumors, largely due to tumor antigen heterogeneity, immune evasion mechanisms, and poor infiltration and persistence. In this recent study, Guerrero et al endeavor to improve the efficacy of human CAR T cells by overexpressing the glucose transporter GLUT1 and show that GLUT1 overexpressing CAR T cells have improved capacity to persist and control tumor burden in vivo.

The oral epithelium, a dynamic interface constantly facing environmental challenges, relies on intricate molecular pathways to maintain its homeostasis. This comprehensive review delves into the nuanced interplay between T-lymphocytic cells (T cells) and RNA-binding proteins (RBPs) within the oral epithelium, elucidating their roles in orchestrating immune responses and influencing tissue plasticity. By synthesizing current knowledge, we aim to unravel the molecular intricacies that govern this interplay, with a focus on potential therapeutic implications for oral health and diseases. Understanding the regulatory networks shaped by T cells and RBPs in the oral epithelial microenvironment holds promise for innovative strategies in managing conditions associated with epithelial dysfunction.

The nucleotide-binding domain, leucine-rich repeat, and pyrin domain containing-protein 3 (NLRP3) inflammasome is a multiprotein complex that plays a critical role in the innate immune response to both infections and sterile stressors. Dysregulated NLRP3 activation has been implicated in a variety of autoimmune and inflammatory diseases, including cryopyrin-associated periodic fever syndromes, diabetes, atherosclerosis, Alzheimer's disease, inflammatory bowel disease, and cancer. Consequently, fine-tuning NLRP3 activity holds significant therapeutic potential. Studies have implicated several organelles, including mitochondria, lysosomes, the endoplasmic reticulum (ER), the Golgi apparatus, endosomes, and the centrosome, in NLRP3 localization and inflammasome assembly. However, reports of conflict and many factors regulating interactions between NLRP3 and subcellular organelles remain unknown. This review synthesizes the current understanding of NLRP3 spatiotemporal dynamics, focusing on recent literature that elucidates the roles of subcellular localization and organelle stress in NLRP3 signaling and its crosstalk with other innate immune pathways converging at these organelles.

Norovirus is a leading cause of gastroenteritis worldwide. The factors required for the life cycle and pathogenesis of norovirus in humans remain unclear. Mouse models of norovirus infection have been widely used to explore the crosstalk between norovirus and the host. The circadian clock entrains biological processes and behaviors including eating and sleeping in response to day-night cycles. How the mucosal immunity is diurnally programmed in response to norovirus infection remains largely unknown. Here, we provide procedures for preparing a murine norovirus strain CR6 and for infection in mouse models under normal day/night light cycles or jet-lag conditions. We also present procedures to quantify viral copies and antiviral response transcripts in host tissues. These protocols will help facilitate studies of norovirus infection and immunometabolic responses from the circadian perspective.

Carotenoids are a diverse group of lipids produced by photosynthetic organisms, and therefore, these compounds are major components of healthy diets. Carotenoids are among the most extensively studied micronutrients to date due to their antioxidant and provitamin A properties. β-carotene is one of the most abundant carotenoids in our diet, but more importantly, it is the main vitamin A precursor in humans. This review summarizes the key metabolic steps involved in vitamin A formation in mammals. It also highlights the recent advancements in the bioactive properties of β-carotene and vitamin A in relationship with atherosclerotic cardiovascular disease. We examine the dual effect retinoic acid, the transcriptionally active form of vitamin A, has on lipid metabolism and atherosclerosis development. Finally, we cover recent findings on the immunomodulatory role retinoic acid plays in macrophages and T cells in the context of atherosclerosis development and resolution.

Colorectal cancer (CRC) is highly prevalent, accounting for approximately one-tenth of cancer cases and deaths globally. It stands as the second most deadly and third most common cancer type. Although the gut microbiota has been implicated in CRC carcinogenesis for the last several decades, it remains one of the least understood risk factors for CRC development, as the gut microbiota is highly diverse and variable. Many studies have uncovered unique microbial signatures in CRC patients compared with healthy matched controls, with variations dependent on patient age, disease stage, and location. In addition, mechanistic studies revealed that tumor-associated bacteria produce diverse metabolites, proteins, and macromolecules during tumor development and progression in the colon, which impact both cancer cells and immune cells. Here, we summarize microbiota's role in tumor development and progression, then we discuss how the metabolic alterations in CRC tumor cells, immune cells, and the tumor microenvironment result in the reprogramming of activation, differentiation, functions, and phenotypes of immune cells within the tumor. Tumor-associated microbiota also undergoes metabolic adaptation to survive within the tumor environment, leading to immune evasion, accumulation of mutations, and impairment of immune cells. Finally, we conclude with a discussion on the interplay between gut microbiota, immunometabolism, and CRC, highlighting a complex interaction that influences cancer development, progression, and cancer therapy efficacy.

A recent paper published in Cell Metabolism in August 2024 by Dirk Brenner's laboratory highlights the importance of effectively managing reactive oxygen species (ROS) in gut T_H17 T cells for minimizing the damage caused by intestinal bacterial infection. This commentary will discuss the control of cellular ROS by glutathione and the emerging understanding that neutralizing ROS in immune cells is essential for the individualized functions of different immune subsets. In the case of this study, managing ROS within T_H17 cells in the gut was shown to be essential to sustain the production of IL22 cytokine to maintain gut homeostasis in response to bacterial infection.

Hematopoietic stem cells (HSCs) are the multipotent progenitors of all immune cells. During aging, their regenerative capacity decreases for reasons that are not well understood. Recently, Song et al investigated the roles of two metabolic proteins in age-related HSC dysfunction: CD38 (a membrane-bound NADase) and the mitochondrial calcium uniporter that transports calcium into the mitochondrial matrix. They found that the interplay between these proteins is deranged in aged HSCs, contributing to their diminished renewal capacity. These findings implicate compromised nicotinamide adenine dinucleotide metabolism as underlying HSC dysfunction in aging.

In recent decades, obesity has become a worldwide epidemic. As a result, the importance of adipose tissue (AT) as a metabolically active storage depot for lipids and a key mediator of body-wide metabolism and energy balance has been increasingly recognized. Emerging from the studies of AT in metabolic disease is a recognition of the importance of the adipocyte progenitor cell (APC) population of AT being the gatekeeper of adipocyte function. APCs have the capability to self-renew and undergo adipogenesis to propagate new adipocytes capable of lipid storage, which is important for maintaining a healthy fat pad, devoid of dysfunctional lipid droplet hypertrophy, inflammation, and fibrosis, which is linked to metabolic diseases, including type 2 diabetes. Like other dividing cells, APCs are at risk for undergoing cell senescence, a state of irreversible cell proliferation arrest that occurs under a variety of stress conditions, including DNA damage and telomere attrition. APC proliferation is controlled by a variety of factors, including paracrine and endocrine factors, quality and timing of energy intake, and the circadian clock system. Therefore, alteration in any of the underlying signaling pathways resulting in excessive proliferation of APCs can lead to premature APC senescence. Better understanding of APCs senescence mechanisms will lead to new interventions extending metabolic health.

Immunometabolism is a rapidly developing field that holds great promise for diagnostic and therapeutic benefits to human diseases. The field has emerged based on seminal findings from in vitro and ex vivo studies that established the fundamental role of metabolism in immune cell effector functions. Currently, the field is acknowledging the necessity of investigating cellular metabolism within the natural context of biological processes. Examining cells in their native microenvironment is essential not only to reveal cell-intrinsic mechanisms but also to understand how cross-talk between neighboring cells regulates metabolism at the tissue level in a local niche. This necessity is driving innovation and advancement in multiple imaging-based technologies to enable analysis of dynamic intracellular metabolism at the single-cell level, with spatial and temporal resolution. In this review, we tally the currently available imaging-based technologies and explore the emerging methods of Raman and autofluorescence lifetime imaging microscopy, which hold significant potential and offer broad applications in the field of immunometabolism.