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T-cell receptor recognition of cognate peptide-MHC leads to the formation of signalling domains and the immunological synapse. Because of the close membrane apposition, there is rapid exclusion of CD45, and therefore LCK activation. Much less is known about whether spatial regulation of the intracellular face dictates LCK activity and TCR signal transduction.
View Article and Find Full Text PDFMmuPV1 infection of Tmc6/Ever1 or Tmc8/Ever2 deficient FVB mice as a model of βHPV in typical epidermodysplasia verruciformis.
PLoS Pathog
January 2025
Department of Pathology, Johns Hopkins University, Baltimore, Maryland, United States of America.
Typical epidermodysplasia verruciformis (EV) is a rare, autosomal recessive disorder characterized by an unusual susceptibility to infection with specific skin-trophic types of human papillomavirus, principally betapapillomaviruses, and a propensity for developing malignant skin tumors in sun exposed regions. Its etiology reflects biallelic loss-of-function mutations in TMC6 (EVER1), TMC8 (EVER2) or CIB1. A TMC6-TMC8-CIB1 protein complex in the endoplasmic reticulum is hypothesized to be a restriction factor in keratinocytes for βHPV infection.
View Article and Find Full Text PDFHypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.
J Clin Immunol
January 2025
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
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.
View Article and Find Full Text PDFGenetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival.
Nat Commun
January 2025
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.
View Article and Find Full Text PDFA combination treatment with a water extract from Euglena gracilis and anti-PD-1 antibody strongly inhibits growth of lung cancer in mice through stimulating tumor-infiltrating lymphocytes.
Int Immunopharmacol
January 2025
Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, Manhattan, KS 66506, USA. Electronic address:
Here, we investigated the relationship between the attenuation of lung cancer growth due to oral administration of Euglena gracilis water extract (EWE) and T cell stimulation. Orally administered EWE was revealed to increase PD-1 and PD-L1 mRNA and proteins primarily in tumor-infiltrating lymphocytes (TILs), which was correlated with a significant decrease in the tumor weights in mice. A combination treatment with EWE and anti-PD-1 antibody significantly decreased the growth of murine lung tumors more than treatment with either alone by increasing the number of TILs and attenuating T cell exhaustion.
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