Trends in Immunology

Integration of biochemical and physical cues by patrolling CD8+ T cells CD8+ T cell migration is central to host defense, enabling clonal selection, tissue infiltration, and elimination of infected cells. While chemokines guide these cells by activating Rac for F-actin polymerization, recent studies reveal a complementary mechanism through Rho activation. This pathway relies on tissue confinement, which deforms the nucleus, activates the actomyosin network, and allows CD8+ T cells to use physical cues for surveillance without external signals. In this review article, we explore how chemokine- and mechanosensing-dependent pathways guide CD8+ T cell surveillance and introduce a ‘front-’ versus ‘rear-driven’ motility model to illustrate their integration for effective tissue monitoring. Ultimately, the interplay of biochemical and physical cues ensures tissue-specific protection by T cells during homeostasis and inflammation.

Integration of biochemical and physical cues by patrolling CD8+ T cells #immunology

Early bird registration ends today!

We’re offering exclusive in-person 1:1 meetings with Cell Press editors for participants of @CellSymposia #CSImmuneHomeostasis26 in Shanghai, China (May 11–13, 2026).
Early bird registration ends today!
http://dlvr.it/TRKq2z

Two models, one question: how does respiratory syncytial virus cause asthma? De Leeuw et al. conducted human observational and murine studies to establish the combined role of parental aeroallergen sensitization and early-life respiratory syncytial virus infection in asthma development. The findings reveal synergistic effects driving immunological, pathological, and physiological changes resembling asthma, advancing the understanding of disease mechanisms and potential preventive targets.

Two models, one question: how does respiratory syncytial virus cause asthma? #immunology

Secondary bile acids as immune and metabolic mediators Bile acids are cholesterol derivatives, generated by the coordinated intervention of human and bacterial genes, functioning as endogenous ligands for multiple transcription factors and receptors throughout the body. While only two primary bile acids are generated by the human liver, the intestinal microbiota is the source of hundreds of secondary bile acids and microbially conjugated bile acids. Secondary bile acids regulate immune function throughout the body, promote the conversion of thyroid hormone, and regulate energy expenditure in muscle and adipose tissues, ultimately contributing to the beneficial effects of calorie restriction on human health and longevity. Here, we discuss recent advances in our understanding of secondary bile acids, the intestinal microbiota generating them, and their role in immune disorders.

Secondary bile acids as immune and metabolic mediators #immunology

Decidual immune activation by extravillous trophoblasts drives maternal-fetal tolerance and immunity During pregnancy, complex interactions of maternal immune cells and fetal extravillous trophoblasts (EVTs) orchestrate placentation, immune tolerance, and immune defense. This forum article highlights important discoveries and outstanding questions on how the activation of decidual natural killer and T cells, through recognition of key EVT ligands, promotes placentation, tolerance, and immunity.

Decidual immune activation by extravillous trophoblasts drives maternal-fetal tolerance and immunity #immunology

Cytokine specificity in macrophages: JAK-STAT and beyond Macrophages are key in maintaining tissue homeostasis and controlling inflammation. To rapidly adapt their phenotype, they rely on JAK-STAT signaling pathways to convert extracellular cytokine cues into transcriptional responses. Understanding how macrophages interpret disease-associated cytokine environments is therefore key for deciphering how inflammation is resolved or sustained.

Cytokine specificity in macrophages: JAK-STAT and beyond #immunology

Got milk? how T cells shape lactation and beyond Lactation is increasingly recognized as an immune-regulated process. Immune cells shape mammary gland development, coordinate tissue remodeling, and aid in milk production with lasting consequences for maternal health. Here, we summarize recent advances on the roles and dynamics of T cells in the mammary gland during lactation and beyond.

Got milk? how T cells shape lactation and beyond #immunology

Flt3L from interfollicular stroma maintains resident dendritic cells Dendritic cell (DC) maintenance and positioning are essential for their function in lymph nodes. Wu et al. identify gremlin1 (Grem1)+ fibroblastic reticular cells as critical source of niche-specific Fms-like tyrosine kinase 3 ligand (Flt3L) for conventional DC maintenance in health and disease, highlighting stromal cells as key regulators of immunity.

Flt3L from interfollicular stroma maintains resident dendritic cells #immunology

Cell Symposia: Immune regulation of organismal homeostasis: Keeping the middle path

Last chance to submit an abstract and be considered for a short talk @CellSymposia #CSImmuneHomeostasis26 taking place on May 11–13, 2026 in Shanghai, China
Submit here: http://dlvr.it/TQWYrt

Bruce Koppelman interviews Dr. Bing Su about Cell Symposia: Immune regulation of organismal homeostasis: Keeping the middle path

Bruce Koppelman @cp-immunity.bsky.social speaks with Dr. Bing Su (Shanghai Jiao Tong University) about the vision behind @CellSymposia #CSImmuneHomeostasis26 taking place May 11–13, 2026, Shanghai, China.

Watch the interview: http://dlvr.it/TQLQcK

Decoding brain border immunity to enable future therapeutic avenues The brain is no longer viewed as immunologically isolated but as an organ surrounded by dynamic border compartments that coordinate surveillance, drainage, and communication with the periphery. Key interfaces – including the meninges, blood–brain barrier, choroid plexus (ChP), and skull bone marrow – host specialized immune niches that regulate antigen sampling, leukocyte trafficking, and neuroimmune signaling. Recent advances in imaging and in single-cell and spatial profiling have revealed previously unrecognized cell types, migration routes, and barrier specializations that shape central nervous system (CNS) immunity in health and disease. Understanding how these border tissues sense, integrate, and modulate immune activity opens opportunities for therapeutically tuning neuroimmune responses at the brain’s periphery while preserving parenchymal integrity.

Decoding brain border immunity to enable future therapeutic avenues #immunology

Resident T cells in the healthy and multiple sclerosis brain Insights into T-cell biology in the central nervous system (CNS) have evolved from early neuroinflammatory models demonstrating the pathogenic potential of autoreactive T cells to recent human studies defining resident T-cell populations in the healthy and diseased brain. We here discuss advances in postmortem brain tissue processing, flow cytometry, and transcriptional profiling revealing that human brain CD8+ and CD4+ T cells are tissue-resident memory T cells with distinct phenotypes shaped by CNS borders and parenchymal niches. These findings refine our understanding of CNS immune surveillance and provide a framework for dissecting T-cell contributions to multiple sclerosis.

Resident T cells in the healthy and multiple sclerosis brain #immunology

Microglia in systemic neuroimmune communication: functions beyond phagocytosis Bidirectional crosstalk between the immune and nervous systems, via ‘neuroimmune circuits’, regulates homeostatic and inflammatory responses essential for health. Microglia, long-lived brain macrophages, act as key hubs integrating immune signals into coordinated brain responses by shifting into distinct functional states in response to local and systemic cues. In this review, we focus on how environmental signals shape these microglial states, how microglia influence other brain cells through both direct and indirect mechanisms, and emerging evidence of how microglia are impacted by, and respond to, peripheral changes. We highlight microglia as central players in systemic neuroimmune communication, influencing both brain and peripheral health, while outlining recent tools and key knowledge gaps to guide future research into mechanisms of neuroimmune circuit communication.

Microglia in systemic neuroimmune communication: functions beyond phagocytosis #immunology

Tissue-resident regulatory T cells: modulators of local immunity Regulatory T cells (Tregs) have gained renewed attention for their diverse roles beyond immune suppression. This review integrates recent discoveries on how tissue-resident Tregs integrate immune, metabolic, and neural cues to maintain organ homeostasis and regeneration. Across adipose tissue, intestine, brain, and skin, Tregs coordinate local networks that couple immune tolerance with metabolic balance and tissue repair. We further discuss therapeutic advances – including antigen-specific chimeric antigen receptor (CAR)/T cell receptor (TCR) Tregs, interleukin 2 (IL-2) muteins, and metabolic modulation – that aim to harness Tregs for treating autoimmunity and chronic inflammation. Together, these insights highlight Tregs as central interpreters of tissue context and as promising targets for next-generation precision immunotherapy.

Tissue-resident regulatory T cells: modulators of local immunity #immunology

Interleukin-23 biology linking mucosal immunity to autoimmune diseases and cancer Interleukin-23 (IL-23) is a pleiotropic cytokine that maintains the delicate balance between tolerance to commensal microbiota and defense against pathogens at mucosal barriers. When dysregulated, IL-23 becomes a key driver of chronic inflammation, with therapeutics blocking this pathway being successfully harnessed in the clinic. In this review, we discuss recently uncovered biology of IL-23 in the context of mucosal immunity, which intimately links the role of this pathway to the pathophysiology of autoimmunity, chronic inflammation, and emerging functions in cancer. Through the lens of the cell types that respond to IL-23, the engaged effector programs, and the key functions in health and disease, we highlight recent advances and opportunities to better understand the dichotomous outcomes mediated by this cytokine.

Interleukin-23 biology linking mucosal immunity to autoimmune diseases and cancer #immunology

Lactation, tissue-resident immunity, and protection against breast cancer Parity and lactation have long been recognised as protective factors in breast cancer, with notable risk reduction in triple negative breast cancer (TNBC). Recent work by Virassamy et al. suggests a tissue-specific, persistent immune surveillance underpins this effect, particularly in women who have also breastfed.

Lactation, tissue-resident immunity, and protection against breast cancer #immunology

Targeting γδ T cells for immunotherapies against colorectal cancer The advancement of immunotherapy faces significant challenges, including extending its benefits to a growing number of patients and enhancing its efficacy across different tumor types. In this context, γδ T cells emerge as particularly promising candidates owing to their distinctive biological features such as MHC-independent activation, potent cytotoxicity, and capacity to bridge innate and adaptive immunity. Recently, advanced single-cell techniques have allowed detailed γδ T cell characterization in the tumor microenvironment (TME) and have emphasized their heterogeneity, mechanisms of activation, and response to immune checkpoint blockade (ICB). This review provides a comprehensive summary of recent advances in understanding γδ T cells in colorectal cancer (CRC), with a particular emphasis on their prognostic and therapeutic relevance in both primary tumors and metastatic disease.

Targeting γδ T cells for immunotherapies against colorectal cancer #immunology

Group 3 innate lymphoid cells: guardians of intestinal homeostasis Intestinal homeostasis is crucial for overall health, and its maintenance relies on a complex and delicate interplay between intestinal epithelial cells, the gut microbiota, and the immune system. Among immune components, group 3 innate lymphoid cells (ILC3s), which primarily reside in the intestinal microenvironment, play a crucial role in maintaining gut homeostasis. Through the expression of multiple effector molecules such as interleukin (IL)-22 and major histocompatibility complex class II (MHCII), ILC3s orchestrate intestinal epithelial responses and regulate innate and adaptive immunity, thereby collectively promoting a symbiotic host–microbiota relationship, supporting immune tolerance, and providing protection against pathogens. This review summarizes current understanding of ILC3 functions in gut homeostasis, highlights their interactions with the microbiota and other cell types, and outlines how aberrant ILC3 activity contributes to disease pathogenesis.

Group 3 innate lymphoid cells: guardians of intestinal homeostasis #immunology

A novel mechanism of immunoevasion by ER+ breast cancer #immunology

Immune cellular homeostasis and its breakdown at the maternal–fetal interface #immunology

Neuronal inflammasomes: balancing immunity, neuroinflammation, and homeostasis Recent discoveries reveal that inflammasome signaling in neurons extends beyond host defense to influence fundamental aspects of brain function, including synaptic plasticity, axon remodeling, and exosome-mediated intercellular communication. This review explores how basal neuronal inflammasome activity contributes to central nervous system (CNS) homeostasis and how heightened signaling in neurons drives neuroinflammatory and degenerative processes. Understanding these dual roles of neuronal inflammasomes provides new insights into neuroimmune crosstalk and identifies potential targets for modulating repair and inflammation in CNS injury and disease.

Neuronal inflammasomes: balancing immunity, neuroinflammation, and homeostasis #immunology

1918 Influenza victims crowd into an emergency hospital CREDIT AP Photo National Museum of Health

To effectively treat long #COVID, we must learn from historical chronic illnesses, medical researchers say. spkl.io/63328AgJFr

Akiko Iwasaki, Christine Miller, Janna Moen
@cp-trendsimmuno.bsky.social

News Release 4-Dec-2025

To treat long COVID, we must learn from historical chronic illnesses, medical researchers say

www.eurekalert.org/news-release...

Lots of discussion of ME/CFS in full paper

#PAIS #MEcfs #LongCovid

🧬🍽️ Your macrophages may be carrying your mother’s metabolic history!
In our @cp-trendsimmuno.bsky.social article, we discuss how maternal diet programs lifelong immune function.
authors.elsevier.com/sd/article/S...
#ImmuneMemory #Macrophages #MaternalNutrition #DOHaD #EarlyLifeProgramming

Maternal diet shapes the development and identity of tissue-resident macrophages The developmental origins of health and diseases concept posits that early-life exposure to environmental adversities increases risks for diverse noncommunicable and infectious diseases. Among these adversities, maternal malnutrition is a critical determinant of offspring health trajectories. Maternal malnutrition from preconception to lactation can durably alter cellular and tissue function in the offspring. We propose that tissue-resident macrophages (TRMs) act as central mediators of this developmental programming. Seeding tissues during embryogenesis, integrating metabolic and hormonal signals, and persisting throughout life, TRMs can encode maternal nutritional states into lasting tissue adaptations. We summarize how specific maternal diets program distinct TRM subsets and how programmed TRMs link maternal nutritional statuses to disease susceptibility. TRMs may offer early intervention targets to improve offspring health.

Maternal diet shapes the development and identity of tissue-resident macrophages #immunology

IEL–IEC circuit in barrier immunity and beyond The intestinal epithelium functions as an immune–metabolic interface, integrating environmental signals to maintain systemic homeostasis. Intraepithelial lymphocytes (IELs), interspersed within the epithelial layer, form a highly interactive network with intestinal epithelial cells (IECs) to coordinate barrier defense, immune tolerance, and metabolic regulation. IECs orchestrate IEL development, positioning, and functional programming. Reciprocally, IELs modulate epithelial physiology, nutrient uptake, and epithelial repair. Dysregulation of the IEL–IEC unit contributes to intestinal and extraintestinal pathologies. This review discusses current advances in IEL–IEC bidirectional communication, highlighting the influences of diet, microbial metabolites, and immune checkpoints on this interface. We propose a paradigm in which the IEL–IEC interplay functions as a key immunometabolic regulatory unit and represents a promising therapeutic target for systemic diseases.

IEL–IEC circuit in barrier immunity and beyond #immunology

The lingering shadow of epidemics: post-acute sequelae across history The SARS-CoV-2 pandemic has drawn global attention to post-acute infection syndromes (PAIS), with millions affected by post-acute sequelae of COVID-19 (PASC, or Long COVID). While Long COVID is newly defined, PAIS have been described for over a century following epidemic infections. Multiple pathogens – including influenza, Epstein-Barr virus, and Borrelia burgdorferi, among others – can precipitate persistent, poorly understood symptoms. Chronic illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have long been linked to infectious triggers. This recurring association highlights critical knowledge gaps and underscores the need for systematic investigation. Unlike prior pandemics, the current era offers advanced technologies and analytic tools to address these gaps. Defining the biology of Long COVID may yield broader insights into host–pathogen interactions and mechanisms of chronic illness.

The lingering shadow of epidemics: post-acute sequelae across history #immunology

Glycolytic diversity drives immune complexity in cancer 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.

Glycolytic diversity drives immune complexity in cancer #immunology

Auguries of adaptivity: LES γδ TCR ligand recognition revisited Identification of antigenic ligands for the γδ T cell receptor (TCR) has remained a highly challenging goal since the emergence in the 1980s of γδ T cells as a distinct immune compartment. In a significant advance more than 12 years ago, endothelial protein C receptor (EPCR), a cell-surface-expressed major histocompatibility complex (MHC)-like protein that binds phospholipids, was identified as the first ligand for a human γδ TCR to be validated by direct binding experiments: a finding that undoubtedly posed more questions than it answered. In this review we discuss how features of this single clonotypic specificity anticipated insights into adaptive-like human γδ T cell biology that emerged in subsequent investigations, and we highlight recent findings about EPCR that point towards the relevance of such responses in anti-pathogen and potentially anti-tumour immunity.

Auguries of adaptivity: LES γδ TCR ligand recognition revisited #immunology

Get with the program: regulation of T cell death #immunology