Chimeric antigen receptor (CAR) T cell therapy has been associated with acute neurotoxicity syndromes and with longer-term neurological symptoms. In Cell, Geraghty et al. identify the mechanism behind long-term cognitive symptoms after CAR T cell therapy. The authors used patient-derived xenograft mouse models of central nervous system (CNS) and non-CNS cancers, and an immunocompetent mouse model of

Patients with peritoneal metastasis can develop ascites, the collection of fluid in the abdomen. Although this has been linked to tumor growth, the mechanisms by which ascites suppresses anti-tumor immunity are unclear. In Science Immunology, Slattery et al. find that natural killer (NK) cells uptake lipids from ascites and this drives NK cell dysfunction, which may contribute to immune suppression

Glioblastoma (GBM) is an aggressive tumor with limited treatment options. In Nature, Faust Akl et al. show that both human and mouse GBM indirectly suppress adaptive immune antitumor responses by inducing TRAIL expression in astrocytes. TRAIL+ astrocytes trigger CD4+ and CD8+ T cell apoptosis by cognate interaction with DR4 and DR5 death receptors expressed on their cell surface. In the tumor microenvironment

Neuronal synaptic plasticity in the hippocampus is required for the formation of new neuronal connections during memory formation. In Immunity, Zengeler et al. report that inflammasome activation in hippocampus astrocytes regulates hippocampal plasticity, synaptic protein density, neuronal activity, extracellular matrix abundance and IL-33 production. ASC specks and cleaved caspase-1 and IL-18 — but

A preprint by Ellul et al. reports that maternal immune activation of mice imprints regulatory T cell dysfunction in offsping that drives autism-like behaviours.

(Immunity 58, 1236–1253.e1–e8; May 13, 2025)

A study describes how maternal immune activation can lead to neurodevelopmental deficits in offspring, through a mechanism involving granzyme B release by decidual natural killer cells.

Five recent papers identify the RORγt+ antigen-presenting cells that induce food-antigen-specific regulatory T cells and establish food tolerance.

Interferonopathies drive autoimmunity but can also impair host responses to pathogens, including viral infections. To better understand viral susceptibility of patients with STAT1 gain-of-function (GOF) mutations, we generated conditional knockin mouse models to elucidate disease mechanisms and relevance of different immune subsets. Virally infected Stat1 GOF mice exhibited impaired early IFN-γ production

CD4 + T cells are indispensable for optimal immunity to Mycobacterium tuberculosis ( M.tb ), a pathogen that triggers tuberculosis (TB) in humans. M.tb -specific human CD4 + T cells are known to polarize toward an interferon-γ (IFN-γ)–producing, CCR4 − CCR6 + CXCR3 + T-bet + RORγT + T helper 1* cell (T H 1*cell) memory phenotype. We report that autosomal recessive deficiency of the human lymphocytic

(Immunity 56, 2736–2754.e1–e8; December 12, 2023)

BACKGROUND Mast cells and macrophages are tissue-resident immune cells frequently found in close proximity in barrier organs. Macrophages show high plasticity and microenvironmental factors, such as cytokines, can influence their phenotype. Mast cells are central in allergic reactions where allergens cause mast cell activation via antigen-specific IgE antibodies and the release of a multitude of inflammatory

BACKGROUND Anti-type 2 cytokine therapies represent promising interventions for chronic itch; however, their precise mechanisms in restoring nerve architecture and mitigating inflammation and pruritus remain incompletely understood. OBJECTIVES This study aimed to elucidate the mechanistic roles of IL-4, IL-13, and IL-31 in the pathophysiology of itch associated with type 2 inflammatory skin diseases

BACKGROUND Macrophages (Mphs) exhibit high heterogeneity and plasticity, which is essential for their multifaceted roles in host defense and tissue regeneration. Mast cells (MCs) respond rapidly to injury or infection by releasing intact secretory granules, thereby initiating and potentiating innate and adaptive immunity. OBJECTIVE Since MCs reside in close proximity to Mph in the skin, we decoded

T cell therapy efficacy can be compromised if cytokine-induced Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling is dysregulated or insufficient to sustain functionality. Here, we demonstrate that LCK kinase activity can be recruited to noncanonical protein substrates to directly activate targeted STAT proteins in T cells. STAT activation was accomplished by engineering

The immune response exhibits strong circadian rhythmicity, with enhanced bacterial clearance often synchronized with an organism’s active phase. Despite providing the bulk of cellular antibacterial defense, the neutrophil clockwork is poorly understood. Here, we used larval zebrafish to explore the role of clock genes in neutrophils during infection. Per2 was required in neutrophils for reactive oxygen

A preprint by Cheng et al. identifies the proton-activated chloride channel PAC as a negative regulator of phagosomal acidification in macrophages.

Asthma is a complex and chronic respiratory condition that affects both adult and pediatric populations. Several asthma endotypes have been described; they include endotypes characterized by TH2 cell inflammation, response to viral infection, and exposure to air pollution. Recent evidence has revealed a novel endotype of pediatric asthma, termed the frequent exacerbator (FE) endotype, which is characterized

BACKGROUND Early infancy is marked by high susceptibility to severe viral respiratory infections and reduced protective antibody responses, making rapid development of local airway immunity essential. Despite this, the developmental dynamics of human airway B-cells and their interaction with airway epithelial cells (AECs) in early life remain poorly understood. OBJECTIVE To study the developmental

BACKGROUND In atopic dermatitis (AD), epidermal disease hallmarks are driven by a complex cutaneous inflammatory milieu that varies between patients. How these variable inflammatory signals affect cellular and molecular epidermal AD phenotypes is difficult to study in vivo. OBJECTIVE We aimed to unravel which AD-associated cytokines drive specific epidermal disease hallmarks. METHODS We utilized primary

BACKGROUND The nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) pathway is a key regulator of immune responses, cell survival, and proliferation. Dysregulation of this signaling pathway is implicated in various human diseases, including inborn errors of immunity. OBJECTIVE We describe the clinical heterogeneity in 16 patients from 4 unrelated families with missense variants in

Helminth infections, particularly in developing countries, remain a notable health burden worldwide. Group 3 innate lymphoid cells (ILC3s) are enriched in the intestine and play a critical role in immunity against extracellular bacteria and fungi. However, whether ILC3s are involved in intestinal helminth infection is still unclear. Here, we report that helminth infection reprograms ILC3s, which, in

Interactions between the nervous and immune systems are critical to healthy physiology and are altered in many human diseases. Many of the major players in type 2 immune responses, including type 2 lymphocytes and cytokines, mast cells, and immunoglobulin E, have been implicated in neuronal function and behavior. Conversely, neurons in both the central and peripheral nervous systems can affect type

Development of type 1 conventional dendritic cells (cDC1s) underlies the capacity to generate antiviral and antitumor immune responses. Here, we identify the basis for cDC1 development from its earliest progenitors, determining the hierarchy of several required transcription factors and uncovering a series of mandatory cis interactions between constituent enhancers within the Irf8 superenhancer. We

BACKGROUND Immune cell metabolism and metabolic end-products influence the nature and magnitude of immune responses. Various autoimmune and inflammatory diseases are associated with dysregulated cellular metabolism. Intravenous immunoglobulin (IVIG), a therapeutic pooled normal IgG, is extensively used for the immunotherapy of a wide-range of autoimmune and inflammatory diseases. Although several cellular