Toll Like Receptor
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2023 ◽  
Vol 83 ◽  
Author(s):  
L. M. Barbosa ◽  
M. B. Santiago ◽  
V. T. Moretto ◽  
D. Athanazio ◽  
D. Takahashi ◽  
...  

Abstract Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud’s arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.


Livers ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 15-29
Author(s):  
Emilio Flint ◽  
Evangelos Triantafyllou ◽  
Christine Bernsmeier

TAM receptors (Tyro3, Axl and MerTK) are a family of tyrosine kinase receptors that are expressed in a variety of cell populations, including liver parenchymal and non-parenchymal cells. These receptors are vital for immune homeostasis, as they regulate the innate immune response by suppressing inflammation via toll-like receptor inhibition and by promoting tissue resolution through efferocytosis. However, there is increasing evidence indicating that aberrant TAM receptor signaling may play a role in pathophysiological processes in the context of liver disease. This review will explore the roles of TAM receptors and their ligands in liver homeostasis as well as a variety of disease settings, including acute liver injury, steatosis, fibrosis, cirrhosis-associated immune dysfunction and hepatocellular carcinoma. A better understanding of our current knowledge of TAM receptors in liver disease may identify new opportunities for disease monitoring as well as novel therapeutic targets. Nonetheless, this review also aims to highlight areas where further research on TAM receptor biology in liver disease is required.


2022 ◽  
Author(s):  
Jong-hoon Lee ◽  
Seongcheol Cho ◽  
Badar Kanwar ◽  
Keum-ho Lee ◽  
Tuan Ngoc Minh Nguyen ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated inflammasome diseases. Moreover, its pathophysiology involves the angiotensin-converting enzyme 2 (ACE2) receptor, Toll-like receptor 4 (TLR4) pathway, neuropilin‑1 pathway, inflammasome activation pathway, sterile alpha motif (SAM) and histidine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization pathway, cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway, spike protein/inflammasome-genetic pathway, and immunological memory engram pathway. Therefore, it is necessary to prescribe anticatalytic treatments to alleviate the SARS-CoV-2 inflammasome, immunologic engram, and spike protein levels.


2022 ◽  
Author(s):  
Yong-Zheng Zhang ◽  
ZHANG Yong-Zheng ◽  
LI Meng-Jia ◽  
WU Yang ◽  
Lu-Feng CHENG

Abstract Background At present, scholars believe that severe COVID-19 is related to a variety of basic diseases, and we also observe this point using multi-omics method. The latest sequencing data of severe COVID-19 patients were combined to analyze the pathological mechanism, and pharmacological experimental research on local drugs was conducted, and a compound ingredient was found to have potential medicinal value. Results Here, we observed, for patients with severe COVID-19 disease, the differential miRNA expression is mainly low but having higher expression of mRNA. These differential mRNA expressions are associated with the activation of inflammatory pathways and ultimately with hypoxia and coagulation. Using database analysis, we found that Yi Xin Tong Mai Granule(YXTMG) might regulate COVID-19 through Toll-like receptor signaling pathway by acting on different immune targets. We found a new molecular mechanism for COVID-19 to turn the crisis around, the down-regulated miR-181a-5p mediates the up-regulation of PLAU and SERPINE1 molecules to cause cardiovascular adverse events, and YXTMG may prevent it. At the same time, molecular docking indicated that the its various components have anti-inflammatory activity. In vitro studies, we confirmed that YXTMG had antioxidant and anti-inflammatory activities. Conclusions The study has supplemented the potential mechanism for the conversion of mild to critical COVID-19 disease and screened the Chinese medicines for improving these factors, providing methodological reference for disease pathology and drug development.


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Inhye Park ◽  
Michael E. Goddard ◽  
Jennifer E. Cole ◽  
Natacha Zanin ◽  
Leo-Pekka Lyytikäinen ◽  
...  

AbstractMacrophages are integral to the pathogenesis of atherosclerosis, but the contribution of distinct macrophage subsets to disease remains poorly defined. Using single cell technologies and conditional ablation via a LysMCre+Clec4a2flox/DTR mouse strain, we demonstrate that the expression of the C-type lectin receptor CLEC4A2 is a distinguishing feature of vascular resident macrophages endowed with athero-protective properties. Through genetic deletion and competitive bone marrow chimera experiments, we identify CLEC4A2 as an intrinsic regulator of macrophage tissue adaptation by promoting a bias in monocyte-to-macrophage in situ differentiation towards colony stimulating factor 1 (CSF1) in vascular health and disease. During atherogenesis, CLEC4A2 deficiency results in loss of resident vascular macrophages and their homeostatic properties causing dysfunctional cholesterol metabolism and enhanced toll-like receptor triggering, exacerbating disease. Our study demonstrates that CLEC4A2 licenses monocytes to join the vascular resident macrophage pool, and that CLEC4A2-mediated macrophage homeostasis is critical to combat cardiovascular disease.


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