ILC2s promote inhibitory synapse formation in the postnatal mouse brain through the production of IL-13.

Several recent reports have demonstrated that B cell-targeting chimeric antigen receptor (CAR) T cells offer a viable treatment option for patients with autoantibody-mediated autoimmune diseases. To present additional data on this therapy and discuss strategies for more efficient clinical translation, leading experts in CAR T cell therapy for autoimmunity from various countries, including China, Germany

T cell immunoglobulin and mucin domain–containing protein 3 (TIM-3) is an immune checkpoint that has critical roles in immune exhaustion. However, little is known about the mechanisms that regulate TIM-3 surface expression and turnover. Here, we report that human TIM-3 is palmitoylated by the palmitoyltransferase DHHC9 at residue cysteine 296 (Cys 296 ). Palmitoylation stabilized TIM-3 by preventing

NK cells offer a promising alternative to T cell therapies in cancer. We evaluated IPH6501, a clinical-stage, tetraspecific NK cell engager (NKCE) armed with a non-alpha IL-2 variant (IL-2v), which targets CD20 and was developed for treating B cell non-Hodgkin lymphoma (B-NHL). CD20-NKCE-IL2v boosts NK cell proliferation and cytotoxicity, showing activity against a range of B-NHL cell lines, including

Asthma has been increasingly recognized as a heterogeneous disease; however, many patients with asthma suffer from allergic asthma. While inhaled corticosteroids and other inhalers have been integral in treating many symptoms of asthma, these medications do not completely address the underlying mechanism of the disease. Pediatric asthma imposes a substantial burden on patients and the healthcare system

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition characterized by type 2 (T2) immune responses with significant impacts on quality of life and healthcare costs. Local IgE production in nasal polyp tissue plays a key role in the T2 inflammatory cascade. Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment for some patients with CRSwNP regardless

The epidemiology of COVID-19 in children has evolved throughout the pandemic, with initially low infection rates rising significantly due to the emergence of the more transmissible Omicron variant. Adolescents, children from ethnic minorities and lower-income households, and those with obesity are at increased risk of contracting SARS-CoV-2 infection. The immune response in children leads to milder

BACKGROUND IgG can mediate murine and human systemic anaphylaxis (SA). The roles of mast cells (MCs) and histamine in IgG-mediated anaphylaxis are controversial for mice and have not been studied in vivo for humans. We now investigate these issues. METHODS Actively or passively sensitized wild-type and immune-deficient mice were induced to develop anaphylaxis by i.v. antigen challenge. Anaphylaxis

Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age

BACKGROUND An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD. OBJECTIVE To determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms based on multi-omics analyses. METHODS Latent class trajectory analysis was

Self-reported food allergies (FAs) affect approximately 8% of the US pediatric and approximately 10% of the adult population, which reflects potentially disproportionate increases among ethnically and racially minoritized groups. Multiple gaps and unmet needs exist regarding FA disparities. There is reported evidence of disparities in FA outcomes, and the FA burden may also be disproportionate in low-income

The role of type I interferon (IFN-I) in systemic lupus erythematosus (SLE) is well documented, but the role of interleukin (IL)-1β remains elusive. In this issue of Immunity, Caielli et al. identified an SLE monocyte population coproducing IL-1β and IFN-I and described how mitochondrial nucleic-acid-containing RBCs engage cGAS/STING, RIG-I, MDA5, and NLRP3 for unconventional IL-1β release.

Tissue-resident memory T (TRM) cells adapt to diverse environments, providing local long-term protection. In this issue of Immunity, Obers et al. and Raynor et al. demonstrate how diet, commensals, and host factors determine TRM cell development, maintenance, and function across tissues.

The mechanisms by which oncogenic mutations and anatomical locations work together to influence the immune environment within tumors are not well understood. In this issue of Immunity, Ross et al. show that H3.3K27M diffuse midline gliomas (DMGs) are enriched with disease-associated myeloid cells (DAMs). Myeloid-targeted strategies reprogram DAMs to a homeostatic state, reduce myeloid infiltration

Insufficient influx of T cells into the tumor microenvironment, including brain metastasis, dramatically limits efficacy of conventional immunotherapy. In this issue of Immunity, Messmer et al. interrogate spatiotemporal dependencies of melanoma brain metastasis T cell infiltration by intravital microscopy. They find that T cells enter these brain tumors through peritumoral venous vessels and can be

Resistance to tyrosine kinase inhibitors (TKIs) in lung cancer brain metastasis (LCBM) remains a clinical challenge. Recently in Cancer Cell, Fu et al. reveal how TKIs reshape the immune microenvironment of LCBM and propose CTLA4 blockade as a promising strategy to overcome resistance.

BACKGROUND The nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens, and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and

LRRK2 polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinson’s disease and Crohn’s disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeutic strategy being explored for Parkinson’s disease, may also benefit patients with CD. Paneth cell homeostasis is tightly regulated by autophagy, and their dysfunction

Endogenous retroviruses (ERVs), comprising a substantial portion of the vertebrate genome, are remnants of ancient genetic invaders. ERVs with near-intact coding potential reactivate in B cell–deficient mice. To study how B cells contribute to host anti-ERV immunity, we used an antigen-baiting strategy to enrich B cells reactive to ERV surface antigens. We identified ERV-reactive B-1 cells expressing

Immune responses require complex, spatially-coordinated interactions between immune cells and their tissue environment. For decades, we have imaged tissue sections to visualise a limited number of immune-related macromolecules in situ, functioning as surrogates for cell types or processes of interest. However, this inevitably provides a limited snapshot of the tissue's immune landscape. Recent developments

BACKGROUND Amlitelimab, a fully human nondepleting monoclonal antibody targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD). OBJECTIVE This trial evaluated the efficacy and safety of amlitelimab in adults with AD. METHODS In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (NCT05131477), patients received

BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NPs) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear. OBJECTIVE To reveal the roles

BACKGROUND The mental health conditions of allergic diseases has been investigated, but the consistency and magnitude of their effects are unclear. The aim of this umbrella review is to systematically evaluate the published evidence on allergic diseases and mental health conditions to establish a new hierarchy of evidence and identify gaps in this area of research. METHODS We systematically searched

BACKGROUND Ataxia Telangiectasia (A-T) is a DNA repair disorder with cancer predisposition. OBJECTIVE Characterize the prevalence and outcomes of hematologic and solid cancers and treatment-associated toxicities in individuals with A-T. METHODS Data was retrospectively analyzed from the Johns Hopkins Ataxia Telangiectasia Clinical Center cohort. Cumulative incidence and standardized incidence ratios

BACKGROUND Therapies targeting interleukin-5 (IL-5) or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma. OBJECTIVE To investigate the impact of anti-IL-5 and anti-IL-5Rα biological therapies on mast cells (MCs) and their progenitors. METHODS Surface IL-5Rα expression was investigated on MCs and their progenitors in mouse lungs and bone marrow, and in human

BACKGROUND There have been multiple reports of the anti-IL4Rα agent, dupilumab, as associated with the onset and/or progression of cutaneous T-cell lymphoma (CTCL). OBJECTIVE We sought to evaluate safety signals associated with dupilumab, with a focus on CTCL, and to evaluate possible underlying mechanism(s) for the potential association. METHODS First, we used the FDA pharmacovigilance database, FAERS

BACKGROUND T helper 2 (Th2) cells crucially contribute to the pathogenesis of atopic dermatitis (AD) by secreting high levels of IL-13 and IL-22. Yet, the upstream regulators that activate Th2 cells in AD skin remain unclear. IL-18 is a putative upstream regulator of Th2 cells as it is implicated in AD pathogenesis and has the capacity to activate T cells. OBJECTIVE To decipher the role of IL-18 in

Food Protein-Induced Enterocolitis (FPIES) is a non-IgE mediated GI food allergy characterized by delayed, protracted vomiting, accompanied by lethargy and pallor, usually 1-4 hours following ingestion of the food allergen. The pathophysiology of FPIES remains unknown and currently there are no diagnostic biomarkers available to assess disease activity or its resolution. Over the last two decades,

BACKGROUND Clinical trials and real-world experience have provided evidence for the clinical benefit of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exists regarding the impact of mepolizumab on airway remodelling. OBJECTIVE We thus investigated the effect of mepolizumab on airway structural remodelling in patients treated for severe asthma in routine clinical care. METHODS

Initiation of newborn screening (NBS) programs in Europe dates back to the 1960s. One of the most recent expansions of NBS programs was the addition of severe combined immunodeficiency (SCID) based on detection of T-cell receptor excision circles (TRECs). In this review, we present an overview of the current situation in Europe. To avoid a biased overview based on only published results, a 37-item