Advances in T cell biology have revealed heterogeneity among T cell populations that is not captured by existing general nomenclature. This issue has caused an ad hoc broadening of core T cell subset definitions and the...Advances in T cell biology have revealed heterogeneity among T cell populations that is not captured by existing general nomenclature. This issue has caused an ad hoc broadening of core T cell subset definitions and the invention of new subset designations that have not been uniformly delineated. To address this issue, in this Consensus Statement, we propose guidelines that serve three goals. First, they advocate that primary research reports define the experimental basis by which relevant subsets are designated in the methods section of each study. Second, they provide standardized definitions for existing subset designations in popular use, and common experimental criteria for defining each subset are noted. Last, they present an alternative 'modular nomenclature' paradigm. The newly proposed modular nomenclature eschews conceptualization of antigen-experienced T cells as belonging to a few idealized subsets, and the nomenclature instead simply indicates individual biological properties present in a T cell population with brief descriptors. Collectively, these guidelines intend to enhance transparency in the literature while facilitating clearer communication of findings and concepts to researchers, students and clinicians.
Since the discovery of the segmented shape of the neutrophil nucleus, scientists have pondered its physiological relevance. Yet, to this day, neither the functional relevance nor the molecular mechanisms underlying the s...Since the discovery of the segmented shape of the neutrophil nucleus, scientists have pondered its physiological relevance. Yet, to this day, neither the functional relevance nor the molecular mechanisms underlying the segmentation of the neutrophil nucleus are fully understood. Some experimental evidence supports a role of nuclear segmentation in efficient neutrophil migration but its impact on key neutrophil functions, such as phagocytosis, degranulation or production of reactive oxygen species, remains unclear. Nonetheless, the role of nuclear shape in remodelling chromatin and regulating gene expression has high potential for biological and translational relevance. This Review aims to compile and connect the current studies on the neutrophil nucleus, while also discussing studies in other cell types that could inform us about the relevance or mechanisms of nuclear segmentation.
The process of phagocytosis creates intracellular compartments (organelles known as phagosomes) that are central hubs for innate immune sensing of potentially dangerous microorganisms, cells, cellular debris and foreign...The process of phagocytosis creates intracellular compartments (organelles known as phagosomes) that are central hubs for innate immune sensing of potentially dangerous microorganisms, cells, cellular debris and foreign objects. Receptors, enzymes and signalling molecules are specifically enriched in these compartments, wherein they learn everything they can about the phagocytosed material and signal for the cell to mount appropriate responses. The phagosome organelle is also a compartment that facilitates nutrient and metabolite harvesting from internalized materials. This Review explores recent developments in our understanding of phagocytosis as a specific mechanism of innate immune sensing. We discuss efforts to identify the catalogue of proteins that are enriched in different types of phagosomes to learn how these molecules work together to tailor inflammatory and antimicrobial immune responses.
The concept of structural immunity, as defined in this Perspective, posits that the first line of immune defence against foreign agents and tissue damage involves the preventative, physical reinforcement of tissue barrie...The concept of structural immunity, as defined in this Perspective, posits that the first line of immune defence against foreign agents and tissue damage involves the preventative, physical reinforcement of tissue barriers and that this fundamental task can be directly or indirectly regulated by immune cells. Indeed, several types of leukocytes can help build protective barriers when required, potentially either by depositing matrix components themselves in certain circumstances or, more generally, by interactions with canonical structural cells and the existing extracellular matrix. This concept of structural functions of immune cells challenges the rigidity with which mammalian tissue organization and immune defence have been traditionally compartmentalized. Although there is strong momentum in the evidence for structural immunity that has been acquired so far, the field lacks a comprehensive overview of these data as well as a critical evaluation of this concept. Here, we place independent findings from several groups into a working model of immune cells as the architects of tissue barriers, to present a framework on which new concepts and findings in this area can develop.
Winer DA, Du H, Kim J
… +14 more, Chang V, Burke M, Winer S, Costes SV, Frippiat JP, Sams C, Paul AM, Wu H, Ullrich O, Baatout S, Beheshti A, Mason CE, Choukér A, Crucian BE
Nat Rev Immunol
· 2026 Mar · PMID 41102553
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As humans embark on longer and deeper missions into space, it is crucial to understand how spaceflight impacts the immune system. Decades of discoveries, bolstered by recent multiomic analyses, have identified key immune...As humans embark on longer and deeper missions into space, it is crucial to understand how spaceflight impacts the immune system. Decades of discoveries, bolstered by recent multiomic analyses, have identified key immune processes that are affected by the spaceflight environment. These findings form the foundations of the emerging field of 'astroimmunology'. Spaceflight stressors - such as microgravity and galactic cosmic radiation - and other mission-associated variables, including psychological stress and abnormal circadian rhythms, can disrupt or adversely affect immune cell biology. In addition, spaceflight alters host-microbiome interactions, which can increase susceptibility to opportunistic pathogens and viral reactivation. Although ground-based analogues for human spaceflight have provided insights into these stressors individually, their combined effects during spaceflight remain less understood. This Review explores our current knowledge of the effects of spaceflight stressors on the immune system and the clinical implications for human space exploration. It also highlights current and developing countermeasures, including machine-learning approaches, advanced monitoring technologies and standardized biobanking, that can facilitate research into the impact of spaceflight on the immune system. Looking ahead, progressing from low Earth orbit missions to long-term missions to the Moon, Mars and beyond will introduce new challenges, including increased radiation, variable gravity and regolith exposure. We discuss these prospective challenges and outline potential preventive and mitigative strategies for sustaining immune health to enable safe and effective space exploration and habitation of distant worlds.
Chimeric antigen receptor (CAR) T cell therapy holds significant promise for the treatment of cancer; however, its efficacy in solid tumours is substantially hindered by the immunosuppressive tumour microenvironment (TME...Chimeric antigen receptor (CAR) T cell therapy holds significant promise for the treatment of cancer; however, its efficacy in solid tumours is substantially hindered by the immunosuppressive tumour microenvironment (TME). Solid tumours can resist immunotherapy by impairing T cell trafficking, function and persistence. One of the initial obstacles that CAR T cells encounter is the abnormal tumour vasculature, which restricts efficient T cell infiltration, further compounded by a dense extracellular matrix. CAR T cells that do infiltrate the tumours are outnumbered by immunosuppressive cells such as regulatory T cells, myeloid-derived suppressor cells and tumour-associated macrophages. Additionally, tumour cells can contribute to CAR T cell resistance by upregulating immune checkpoint molecules, such as PDL1 and CTLA4, and engage in metabolic competition. In this Review, we discuss how cellular and non-cellular components of the TME impair CAR T cell therapy and consider potential strategies to improve CAR T cell therapies for solid tumours, either by reprogramming the TME or by engineering CAR T cells to resist the immunosuppressive effects of the TME.
Organelles are the internal batteries, gears, actuators, 3D printers and transmitters that drive cell function. Their composition and activity vary between cell types depending on functional demands. In T cells, which ar...Organelles are the internal batteries, gears, actuators, 3D printers and transmitters that drive cell function. Their composition and activity vary between cell types depending on functional demands. In T cells, which are key mediators of immunosurveillance and tumour eradication, organelles are relatively few and function at basal levels when cells are at rest. However, upon activation, they increase in number and size and undergo extensive remodelling to support rapid proliferation, effector differentiation and adaptation to diverse microenvironments, including the tumour microenvironment, thereby enabling efficient clearance of target cells. In this Review, we provide an overview of recent advances in our understanding of how various organelles contribute to T cell-mediated antitumour immunity. We also discuss emerging strategies to modulate organelle functions - from organelle-targeted therapies and their use as cargo delivery systems to the transfer or transplantation of native or synthetic organelles - that have the potential to enhance cancer immunotherapies involving immune-checkpoint blockade or the adoptive transfer of T cells.