Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease in which pancreatic beta cells are selectively destroyed. Although autoimmune diseases are driven by inappropriate adaptive immunity, innate immunity may play a role in the development of T1DM. We investigated the association of the genes for toll-like receptor 2 (TLR2), one of the key surface receptors on innate effectors, with T1DM in Korean patients. Genetic association analyses revealed that the genotype composed of the rare allele (CC) of TLR2 1350 showed weak and protective association with T1DM (OR = 1.7, 95% CI: 1.1-2.7; P < .05) irrespective of the duration of disease, age, and autoantibody status. One of the TLR2 SNP haplotypes, TLR2-Ht4, was strongly associated with T1DM in that those subjects having more than one copy of Ht4 showed strong protection from developing T1DM (OR = 90.5; 95% CI: 13.8-235.7; P < 10(-5)). The TLR2 polymorphisms are associated with T1DM, and distribution differences between T1DM versus controls were not influenced by the HLA genes. There is a close relationship between innate and adaptive immunity.
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Sci Adv
January 2025
Department of Biochemistry, College of Life Science and Biotechnology, Brain Korea 21 Project, Yonsei University, Seoul 03722, Republic of Korea.
Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
Cancer immunotherapy has revolutionized cancer treatment by harnessing the body's immune system to recognize and attack tumors. Over the past 25 years, the use of blocking antibodies has fundamentally transformed the landscape of cancer therapy. However, despite extensive research, agonist antibodies targeting costimulatory receptors such as ICOS, GITR, OX40, CD27, and 4-1BB have consistently underperformed in clinical trials over the past 15 years, failing to meet the anticipated success.
View Article and Find Full Text PDFWhile key for pathogen immobilization, neutrophil extracellular traps (NETs) often cause severe bystander cell/tissue damage. This was hypothesized to depend on their prolonged presence in the vasculature, leading to cytotoxicity. Imaging of NETs (histones, neutrophil elastase, extracellular DNA) with intravital microscopy in blood vessels of mouse livers in a pathogen-replicative-free environment (endotoxemia) led to detection of NET proteins attached to the endothelium for months despite the early disappearance of extracellular DNA.
View Article and Find Full Text PDFBiomark Med
January 2025
Department of Clinical Laboratory, Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China.
Raftlin (raft-linking) protein is an essential component of the lipid raft structure and plays a crucial role in B and T cell signaling pathways. It facilitates B cell receptor (BCR) signaling by promoting calcium mobilization and tyrosine phosphorylation in the cells while colocalizing with BCR on the cell membrane. Interestingly, Raftlin is internalized in lipopolysaccharide-stimulated T cells by colocalization with Toll-like receptor 4 (TLR4), wherein it exerts a similar role as in B cells.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United States.
Introduction: Cigarette smoking is a well-established risk factor for renal dysfunction. Smoking associated with renal damage bears distinct physiological correlations in conditions such as diabetic nephropathy and obesity-induced glomerulopathy. However, the cellular and molecular basis of such an association remains poorly understood.
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