A transposon-derived isoform of the type I interferon (IFN) receptor IFNAR2 can serve as a decoy receptor to regulate IFN signalling.

Yan et al. report the identification of a population of muscle spindle macrophages, which regulate the muscle stretch reflex through glutamate production.

BACKGROUND Chronic erythroderma is a potentially life-threatening condition that can be caused by a variety of diseases, but approximately 30% of cases remain idiopathic, often with insufficient treatment options. OBJECTIVE To establish a molecular disease map of chronic idiopathic erythroderma. METHODS We performed single-cell RNA sequencing combined with T-cell receptor sequencing of blood and skin

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell

Mycobacterium tuberculosis ( M.tb ) is a bacterial pathogen that has evolved in humans, and its interactions with the host are complex and best studied in humans. Myriad immune pathways are involved in infection control, granuloma formation, and progression to tuberculosis (TB) disease. Inflammatory cells, such as macrophages, neutrophils, conventional and unconventional T cells, B cells, NK cells

T cell activity is governed by T cell receptor (TCR) signaling and constrained by immune checkpoint molecules, including programmed cell death protein 1 (PD-1), cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3). The basis for how LAG-3 binds to human leukocyte antigen class II molecules (HLA-II) remains unknown. Here, we present the 3.4-angstrom crystal

RATIONALE Approximately 85% Hereditary angioedema (HAE) attacks are associated with prodromal symptoms. We investigated the clinical effect of treating HAE-C1 inhibitor (HAE-C1INH) Type 1 patients with Conestat Alfa® (recombinant human C1-INH) during their prodrome versus an active swelling episode and associated changes in blood transcriptomic genes and pathways pre- vs. post-treatment. METHODS A

BACKGROUND Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life-limiting, but the mortality of CSU has not been investigated. OBJECTIVE To assess all-cause mortality in CSU patients, risk for comorbidities that are leading causes of death and impact of guideline-recommended urticaria treatments on mortality rates. METHODS This is a retrospective population-based

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies, demonstrating significant clinical efficacy and leading to FDA approval of several CAR-T cell-based products. This success has prompted exploration of CAR-T cell therapy in other disease areas, including autoimmune diseases (AIDs). CAR-T cells targeting B cells have been shown to provide

Despite protective roles in various type of infection and in would healing, T helper (Th)2 cells are drivers of inflammation in allergic asthma. In this issue of Immunity, Zou et al. demonstrate the crucial involvement of hypoxia inducible factor (HIF)2α in promoting the differentiation of inflammatory Th2 cells, suggesting HIF2α as a promising therapeutic target for the treatment of allergic asthma

Hidradenitis suppurativa (HS) is a severe chronic inflammatory skin disease with limited response to therapy. In this issue of Immunity, Yu et al.1 identify skin tertiary lymphoid structures (TLSs) as primary sites for lymphocyte clonal expansion and autoantibody production, driving disease progression, and provide insight into how formation and maintenance of TLS impact therapeutic outcomes.

Rheumatoid arthritis (RA) is driven by antigen-specific T cell responses targeting the joints. MacDonald et al.1 define the range of dendritic cell (DC) populations within joints of RA patients and highlight specific iDC3 and DC2 populations enriched in inflamed RA synovium that promote T cell activation as well as tolerogenic AXL+ DC2s in healthy synovium that are lost in RA.

Central tolerance restricts T cells that target self-antigens. In this issue of Immunity, Abdelfattah et al.1 describe a method to generate self-reactive T cell receptors (TCRs) by directed evolution of non-autoreactive TCRs to recognize self-antigen peptides and demonstrate potential for T cells engineered with such receptors in immunotherapy.

CD4+ T helper (Th) cell differentiation depends on regulatory networks that enforce lineage commitment while suppressing alternative fates. In a recent issue of Nature, Hou et al. reveal that calcitonin gene-related peptide (CGRP) directs Th1 commitment, highlighting neuro-immune crosstalk in T cell fate decisions.

Mast cells are regarded as effectors in immune defense against parasites and venoms and play an essential role in the pathology of allergic diseases. More recently, mast cells have been shown to receive stimuli derived from type 2 immunity, tissue damage, stress, and inflammation. Mast cells then rapidly convert these diverse signals into appropriate, organ-specific protective reflexes that can limit

BACKGROUND Phospholipase Cγ2 (PLCγ2) is an important signaling molecule that receives and transmits signals from various cell surface receptors in most hematopoietic lineages. Variants of PLCG2 cause PLCγ2-associated immune dysregulation (PLAID), a family of conditions that are classified by mutational effect. PLAID with cold urticaria (PLAID-CU) is caused by in-frame deletions of PLCG2 that are dominant

A preprint by Chung et al. presents a framework for the use of transcriptomic and epigenomic data to identify novel transcription factors driving CD8+ T cell states.

BACKGROUND Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations. OBJECTIVES We sought to characterize gut microbiota in children using an enterotyping approach and determine

Correction to: Nature Reviews Immunology https://doi.org/10.1038/s41577-024-01075-9, published online 9 September 2024.

Correction to: Nature Reviews Immunology https://doi.org/10.1038/s41577-024-01075-9, published online 9 September 2024.

Endoglycosidase CU43 removes IgG Fc glycans, inhibits IgG effector functions, and prevents pathology in multiple disease models.

The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using Heligmosomoides polygyrus bakeri ( Hpb ), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)–producing MAIT1 and interleukin-17A (IL-17A)–producing MAIT17 cell subsets in vivo. Whereas T-bet + MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection

Severity of COVID-19 is affected by multiple factors; however, it is not understood how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure affects the control of viral replication. Here, we demonstrate that immune events in the mouse lung closely preceding SARS-CoV-2 infection affect viral control and identify innate immune pathways that limit viral replication. Pulmonary inflammatory

Lymph node IL-2 microniches guide development of T H 2 cells through induction of Blimp-1 expression and an IL-10–positive feedback loop.

(Immunity 57, 2651–2668.e1–e12; November 12, 2024)

Endogenous self-peptides derived from CNS antigens are presented on MHC class II molecules at the borders of the CNS and expand suppressive populations of CD4+ T cells.

Many promising targets for adoptive T cell therapy (ACT) are self-antigens, but self-reactive T cells are generally eliminated during thymic selection or diverted to regulatory phenotypes. To bypass T cell tolerance and obtain potent and safe T cell therapeutics, we developed T-Switch, an in vitro T cell receptor (TCR) engineering platform for the creation, modification, and comprehensive profiling

BACKGROUND Allergic diseases are major causes of morbidity in both developed and developing countries and represent a global burden on health care systems. Allergic sensitization is defined as the production of immunoglobulin E (IgE) specific to common environmental allergens, and it is an important indicator in the assessment of allergic diseases. OBJECTIVES This study aimed to clarify the genetic

Correction to: Nature Immunology https://doi.org/10.1038/s41590-024-02010-9, published online 12 November 2024.

Correction to: Nature Immunology https://doi.org/10.1038/s41590-024-02018-1, published online 18 November 2024.

BACKGROUND STAT3 gain-of-function (GOF) disease presents with lymphoproliferation, autoimmunity, and failure to thrive. While JAK inhibitors have alleviated symptoms, their effects on disease pathogenesis remain unclear. OBJECTIVE We prospectively investigated the clinical, immunological, and transcriptomic responses of four STAT3 GOF patients under long-term ruxolitinib treatment. METHODS We conducted

BACKGROUND CD4+ T cells play essential roles in adaptive immunity. Distinct CD4+ T cell subsets - Th1, Th2, Th17, Th22, T follicular helper and regulatory T cells - have been identified and their contributions to host defence and immune regulation are increasingly well-defined. IL-9 producing Th9 cells were first described in 2008 and appear to play both protective and pathogenic roles in human immunity

BACKGROUND Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). OBJECTIVE We aim to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes. METHODS We recruited children who presented to the emergency room

BACKGROUND Inborn errors of immunity (IEIs) are more than 500 different rare congenital disorders of the immune system characterized by susceptibility to infections and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High throughput sequencing techniques may allow a timely genetic definition. Guidelines for the use and the

Sialylated IgG protects against severe influenza by inducing the transcriptional repressor REST, which dampens the inflammatory response and preserves lung tissue function.

During persistent antigen stimulation, exhausted CD8 + T cells are continuously replenished by self-renewing stem-like T cells. However, how CD8 + T cells adapt to chronic stimulation remains unclear. Here, we show that persistent antigen stimulation primes chromatin for regulation by the redox-sensing KEAP1-NRF2 pathway. Loss of KEAP1 in T cells impaired control of chronic viral infection. T cell–intrinsic

BACKGROUND Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE associated tissue remodeling causes clinical dysphagia, food impactions

Aerosolized particles with a biological origin are called bioaerosols. Bioaerosols from plants, animals, fungi, bacteria and viruses are an important class of environmental exposures that are clinically relevant to asthma. However, there are important differences in the pathways by which various bioaerosols impact asthma. Additionally, differences in individual susceptibility to different bioaerosols