Trends in Immunology最新文献

Sleep is a major driver of waste clearance from the brain, but the mechanisms underpinning brain cleansing during sleep, which are also important for immunological functions, are poorly understood. Recent mouse work by Hauglund et al. shows how oscillatory surges in norepinephrine (NE) during sleep drive vascular pulsation and cerebrospinal fluid (CSF) movement to cleanse the brain.

Lymph node (LN) fibroblastic reticular cells (FRCs) are key regulators of mammalian adaptive immune responses. Together with their deposited extracellular matrix (ECM), FRCs form a reticular network that provides mechanical strength to LNs. Furthermore, the ECM regulates various cell functions including proliferation and differentiation. The ECM is dynamically remodeled in activated LNs, thereby affecting immune cell survival and function. Although both the LN ECM and FRCs can affect immune reactivity, a link between altered LN ECM during an immune response and ECM-producing FRCs is lacking. We explore recent work on the complex interplay between FRCs, ECM, and immune cells in health and disease, and provide guidance for future research to understand the complex regulation of the adaptive immune system within LNs.

Lytic cell death is crucial for antimicrobial and antitumor immunity; however, unchecked pyroptosis drives pathology in sepsis. Wright et al. demonstrate that widespread cell death following pyroptosis is propagated by extracellular vesicles (EVs) carrying gasdermin D (GSDMD) pores that become integrated into the membrane of neighboring cells, driving inflammatory cell death.

Osteoimmunology is an interdisciplinary branch of immunology studying bidirectional interactions between the immune and skeletal systems. Bone marrow is vital for the production of immune cells and is implicated in multiple diseases across all immunology disciplines. Here, we briefly discuss recent progress from the past 5 years in the field and how it impacts our current understanding of health and disease.

Helper innate lymphoid cells (ILCs), comprising groups ILC1, ILC2, and ILC3, possess unique advantages in eliciting rapid immune responses and were recently found to exhibit direct tumor-killing capacities comparable with those of cytotoxic ILCs [natural killer (NK) cells] in humans and mice. Although ILCs are primarily tissue-resident cells, their role in the hematopoietic system is increasingly being recognized. This review provides an overview of ILC ontogeny, as well as the physiological and pathological roles of these cells within the human and murine hematopoietic systems. We recapitulate recent advancements regarding ILC embryonic hematopoietic origin and the dynamic interactions between ILCs and leukemic cells or other immune cell populations, highlighting the dual roles ILCs can play in carcinogenesis. Exploring the functional potential of ILCs can inform the design of rational immunotherapeutic strategies against hematological malignancies.

Fevers are an ancient feature of the inflammatory microenvironment. While fevers may improve the immune response to pathogens, mechanisms are unclear. We explore recent studies of how fever-range temperatures inform mammalian T cell metabolism, differentiation, and stress responses. Recent evidence indicates that metabolic programs initiated by fever are maintained upon return to thermo-normality, potentially providing a lasting benefit. Despite its impact, temperature remains overlooked and warrants further study. This is especially apparent when considering the wide temperature differential between tissues within the body and during inflammatory disease progression. We propose that differences in the metabolic and stress responses between T cell subsets upon thermal stress contribute to determining immune cell makeup and fate during inflammation.

Conventional dendritic cells (cDCs) are sentinels of the mammalian immune system that sense a wide range of danger and homeostatic signals to induce appropriately targeted T cell immune responses. Traditionally classified into two main subsets, cDC1 and cDC2, recent research shows that cDC2s exhibit significant heterogeneity and can be further subdivided. Studies in mice and humans show that, beyond their ontogeny, cDC2s acquire dynamic and tissue-specific characteristics that are influenced by local environmental signals, which impact on their functions during homeostasis, inflammation, and infection. The novel concept is proposed that tissue-derived signals and tissue plasticity can override preestablished developmental programming, thereby redefining developmental trajectories and cDC2 functionality. Ultimately, understanding cDC2 heterogeneity and plasticity has important implications for modulating T cell immunity in health and disease.

Mayassi and colleagues utilized spatial transcriptomics to create a comprehensive blueprint of the mouse gut, exploring its adaptability and resilience under perturbed conditions. Their work highlights the adaptive capabilities of the murine gut's regionalized structure, providing insights into how it functions in a coordinated manner and how it responds to external challenges.

Tumor-infiltrating regulatory T (TI-Treg) cells constitute key components within the tumor microenvironment (TME) to suppress antitumor immunity and facilitate tumor progression. Although multiple therapies have been developed to eliminate TI-Treg cells, most of them exhibit only modest efficacy and harbor risks of inducing immune-related adverse events (irAEs). Recent studies demonstrate that CC chemokine receptor (CCR)8 is highly and specifically expressed on effector TI-Treg cells in mice and humans, highlighting CCR8 as a promising target for selective TI-Treg cell depletion in the treatment of various cancers. Here, we concentrate on the latest understanding of CCR8 regarding its expression, functions, and regulation, and summarize the current landscape of CCR8-targeted therapies. With favorable efficacy and safety, the latter represent an important class of next-generation putative cancer immunotherapies.