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Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.

Nat Commun

January 2025

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, 94143, USA.

The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.

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Skin inflammation and lipid disorder induced by topical application of Mal f 1.

Int Immunopharmacol

January 2025

The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Immunology, The State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China. Electronic address:

Objected: Mal f 1, the first allergen cloned from Malassezia furfur, has been found to have positive IgE reactivity in sera from patients with skin inflammation. In vitro, it has also been shown to induce maturation of dendritic cells and release inflammatory factors. However, its role in skin lipid homeostasis remains largely unexplored.

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Neutrophils play key protective roles in influenza infections, yet excessive neutrophilic inflammation is a hallmark of acute lung injury during severe infections. Phenotypic heterogeneity is increasingly recognized in neutrophil populations; however, how functional variation in neutrophils between individuals determine the diverse outcomes of influenza remains unclear. To examine immunologic responses that may drive varying outcomes in influenza, we infected C57BL/6 (B6) and A/J mice with mouse-adapted influenza A virus A/PR/8/34 H1N1.

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PurposeChimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity.

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Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.

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