Trends in Immunology

Cell intrinsic versus cell extrinsic control of plasma cell longevity 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.

Cell intrinsic versus cell extrinsic control of plasma cell longevity #immunology

Excited to share this highlight of a beautiful study into how myeloperoxidase acts as a chromatin transformer

Reframing IL-27: a central regulator of CD8+ T cell immunity 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 re…

New review out in @cp-trendsimmuno.bsky.social! With @valentinavenzin.bsky.social, we revisit IL-27 as a central regulator of CD8⁺ T cell fate — integrating insights from infection, cancer, and autoimmunity, and outlining its therapeutic potential. www.sciencedirect.com/science/arti...

Beyond the innate immune system: rethinking inflammasomes in multiple sclerosis 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.

Beyond the innate immune system: rethinking inflammasomes in multiple sclerosis #immunology

Reframing IL-27: a central regulator of CD8+ T cell immunity 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.

Reframing IL-27: a central regulator of CD8+ T cell immunity #immunology

Interleukin-22: the hub bridging gut homeostasis and metabolism 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.

Interleukin-22: the hub bridging gut homeostasis and metabolism #immunology

Regulation of intestinal injury via dietary cysteine #immunology

Myeloperoxidase transforms chromatin into an immune weapon Burn et al. reveal a previously unrecognised, non-catalytic function of myeloperoxidase (MPO) in neutrophil extracellular trap (NET) formation; integrating super-resolution microscopy and biochemical approaches, they demonstrated that MPO’s oligomeric state governs chromatin decondensation, redefining MPO as a structural chromatin modifier with implications for diseases driven by dysregulated NETosis.

Myeloperoxidase transforms chromatin into an immune weapon #immunology

Early life determinants of skin-resident T cells 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.

Early life determinants of skin-resident T cells #immunology

Our November issue is online! Check it out 👉https://www.cell.com/issue/S1471-4906(24)X0012-5

#ToPrimeOrNotToPrime, this is the question! Excited for our new review @cp-trendsimmuno.bsky.social with @oceanedufies.bsky.social in which we discuss what is “priming” for the #NLRP3 #inflammasome & how we can harness this knowledge to better control human diseases! #InflammasomePower! #Free 👇👇👇

Thank you for your contribution, Ivan. It was great working with you!✨

Submit your abstract

Are you working on research that challenges the classical function of the immune system? Submit an abstract to @CellSymposia #CSImmuneHomeostasis26 and be considered for a poster or short talk at the meeting in Shanghai, China, May 11–13, 2026 http://dlvr.it/TPFG1G

Post-translational modifications of NLRP3: to prime or not to prime? The NLRP3 inflammasome plays a central role in host defense against microbial infections but also contributes to inflammatory diseases. Functioning of NLRP3 strictly relies on two signals: a ‘priming signal’ that licenses NLRP3 activity and an ‘activation signal’ that triggers inflammasome assembly and downstream caspase-1 activation. The priming signal involves transcriptional upregulation of NLRP3 and diverse post-translational modifications that regulate its stability, subcellular localization, and protein–protein interactions. This multilayered regulation prevents untimely inflammasome activation while enabling its rapid assembly when both priming and activation signals are present. Here, we focus on the complexity of the priming signal and critically analyze and discuss how diverse post-translational modifications cooperate to prime NLRP3, controlling its activity in health and disease.

Post-translational modifications of NLRP3: to prime or not to prime? #immunology

BACH2 and HIV: partners in crime? 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.

BACH2 and HIV: partners in crime? #immunology

Epigenetically programmed identity crisis to combat diffuse large B cell lymphoma Germinal center B cell–like diffuse large B cell lymphoma (GCB-DLBCL) originates from the malignant transformation of germinal center B cells. This process is driven by transcriptional and epigenetic dysregulations, frequently caused by recurrent mutations and chromosomal translocations. These changes lead to a differentiation arrest associated with unchecked proliferation and survival. This review highlights key transcriptional and epigenetic dependencies that sustain the GCB-DLBCL phenotype and identifies therapeutic vulnerabilities. Epigenetic targeting of these vulnerabilities unlocks tumor cells from their differentiation arrest, enabling further yet incomplete differentiation toward an antiproliferative, proapoptotic plasma cell–like or memory B cell–like state. We define this transition as an epigenetically programmed identity crisis, a promising therapeutic strategy to target GCB-DLBCL and potentially other malignancies.

Epigenetically programmed identity crisis to combat diffuse large B cell lymphoma #immunology

DNA methylation and histone modifications drive the trained immunity duration Trained immunity (TRIM) is a de facto form of innate immune memory. While histone modifications contribute to TRIM, their reversible nature and susceptibility to dilution during cell division cannot fully account for its long-term persistence. Here, we propose that DNA methylation patterns, particularly hypomethylation at proinflammatory gene loci, could serve as a key epigenetic mechanism contributing to long-term TRIM. Mechanistically, these hypomethylated states are biochemically stable and faithfully inherited through cell division, acting as a permissive scaffold that enables the rapid accumulation of activating histone marks upon restimulation. This DNA-methylation-mediated process could underpin the durability of TRIM across multiple contexts, including hematopoietic stem cell self-renewal, differentiation from central to peripheral compartments, and autonomy of tissue-resident cells.

DNA methylation and histone modifications drive the trained immunity duration #immunology

Coming of age: mRNA vaccines for orthoflaviviruses Orthoflaviviruses – including dengue, Zika, yellow fever, Japanese encephalitis, and Powassan viruses – are mosquito- and tick-borne members of the family Flaviviridae. Orthoflaviviruses pose major public health threats, with the potential for epidemics and pandemics. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines offer a powerful platform by delivering in vitro-synthesized viral antigen-encoding mRNAs into the host, where they generate proteins that trigger robust immune responses. These synthetic platforms simplify the expression of complex viral glycoproteins, allow rapid and scalable manufacturing that is critical in a pandemic/epidemic scenario, and support multivalent designs to broaden protection. This review highlights recent advancements in mRNA vaccines for orthoflaviviruses and examines how innovations in antigen design and delivery platforms may offer broad, safe, and durable protection against diverse pathogenic orthoflaviviruses.

Coming of age: mRNA vaccines for orthoflaviviruses #immunology

Immunology as a guide to human relationships This essay uses immunology to illuminate human relationships. Moving beyond self/non-self toward danger-based models, it draws parallels between cytokine communication and language, tolerance and forgiveness, microbiota diversity and coexistence. Recognizing these metaphors reveals pathways toward healthier connections within individuals, communities, and societies.

Immunology as a guide to human relationships #immunology

The Janus face of NK cells in neurodevelopment Maternal immune activation (MIA), triggered by infection or inflammation during pregnancy, is a well-recognized risk factor for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). Clinical cohort studies and rodent models suggest that natural killer (NK) cells play a significant role in NDD pathogenesis, but the underlying mechanisms remain poorly defined. Here, we summarize the key immune mediators involved in MIA-induced NDDs, emphasizing microglia as a central hub. We then examine emerging evidence implicating aberrant NK cell activation in ASD, underscoring their overlooked contribution to impaired neurodevelopment. Finally, we discuss potential mechanisms of NK cell–microglia crosstalk in NDDs. Elucidating these interactions in the context of MIA will be crucial for developing preventive and therapeutic strategies against inflammation-driven NDDs.

The Janus face of NK cells in neurodevelopment #immunology

Neuroimmune dynamics and cytokines in traumatic brain injury Traumatic brain injury (TBI) is a leading cause of neurological disability, associated with higher rates of cognitive complications that negatively affect recovery. Myriad cytokine and chemokine pathways propagate the secondary responses to injury. This review discusses the integration of peripheral and central immune cytokine and chemokine signaling cascades after TBI and recovery, with a focus on preclinical work. We first discuss key cytokine and chemokine interactions influencing recovery and long-term deficits. Next, we discuss the major cell types that propagate and respond to the inflammatory process after TBI. Understanding neuroimmune signaling, utilizing recent advances in transcriptomics and immune profiling, with a focus on cytokines and chemokine after TBI reveals therapeutic targets and informs strategies to improve long-term recovery and outcomes.

Neuroimmune dynamics and cytokines in traumatic brain injury #immunology

Dual effects and balanced regulation of cytokines in sepsis Sepsis, a life-threatening condition triggered by infection, disrupts the body’s immune balance and remains a major global health challenge. This forum explores the dual roles of cytokines in sepsis: their overactivation drives ‘cytokine storms,’ and dysregulation leads to immunosuppression. It also discusses regulatory mechanisms for developing targeted therapies.

Dual effects and balanced regulation of cytokines in sepsis #immunology

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

We’re excited to bring you a fresh perspective on the multifaceted role of the immune system at @CellSymposia #CSImmuneHomeostasis26, taking place May 11–13, 2026 in Shanghai, China. Discover more: http://dlvr.it/TNn8c3

🚨 The October issue of Trends in Immunology is live! 🚨
On the cover: T cells transferring membrane proteins like athletes exchanging the baton in a relay run. 🏃🏃‍♂️
🔗Link to the full issue: www.cell.com/issue/S1471-...
#immunology #Tcells #research #trendsinimmunology

In "News from the T cell trogocytosis front" (10.1016/j.it.2025.07.008), we explore the T cell trogocytosis, a form of horizontal protein transfer where T cells “hand off” molecules to each other, much like runners passing a baton in a relay race.

@cp-trendsimmuno.bsky.social

Tile reading "The Nobel Prize in Physiology or Medicine: Read our related articles" Cell Press braned with a NObel Prize medal diplayed on the right hand side.

Congratulations to the 2025 #NobelPrize in Physiology or Medicine winners Drs. Mary Brunkow, Fred Ramsdell, & Shimon Sakaguchi for their discoveries concerning peripheral immune tolerance.

View their related research published in #CellPress journals: spkl.io/63325AVK2R

The dichotomous role of IL-2: tolerance versus immunity Interleukin-2 (IL-2) is a well-known T-cell growth factor, which is traditionally implicated in the agonistic stimulation of immune responses. Recent work, however, has uncovered an unexpected functio...

🎉 Congratulations to #Nobel Prize awardees Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries about peripheral immune tolerance and #tregs
Trends in Immunology had the privilege of featuring their influential research over the years.👉 www.cell.com/trends/immun...

Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation It is controversial how cytotoxic T lymphocyte antigen (CTLA)-4, a co-inhibitory molecule, contributes to immunological tolerance and negative control of immune responses. Its role as an inducer of ce...

🎉 Congratulations to #Nobel Prize awardees Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries about peripheral immune tolerance and #tregs
Trends in Immunology had the privilege of featuring their influential research over the years.👉 www.cell.com/trends/immun...

Fas and FasL in the homeostatic regulation of immune responses Studies of the biological effects of Fas signaling, using transformed cell lines as targets, indicate that ligation of the Fas receptor induces an apoptotic death signal. Chronically activated normal ...

🎉 Congratulations to #Nobel Prize awardees Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries about peripheral immune tolerance and #tregs
Trends in Immunology had the privilege of featuring their influential research over the years.👉
www.cell.com/immunology/f...

A mother's touch: microbial guardians of early immune imprinting The evolution of the fetal immune system within the womb is a delicate balancing act: it is trained to not reject maternal antigens, while equipping itself with ‘learned’ immunity to survive and thrive in the outside world. In this opinion article, we propose that a deliberate maternal touch via immune and nutritional influences, orchestrated, in part, by microbiota-derived components, imprints the fetal immune system with the needed immune memory and epigenetic marks to navigate a far less nurturing outside world, including early microbial colonizers in the newborn’s intestine, pathogens and irritants, and allergens in food. We redefine the hygiene hypothesis to include prenatal maternal microbial exposures, priming fetal immune development for long-term fitness and reduced inflammatory/autoimmune disease risk.

A mother's touch: microbial guardians of early immune imprinting #immunology