FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3134733355> ?p ?o ?g. }

• W3134733355 abstract "Immunoregulatory checkpoint receptors (CR) contribute to the profound immunoparesis observed in alcohol-related liver disease (ALD) and in vitro neutralization of inhibitory-CRs TIM3/PD1 on anti-bacterial T-cells can rescue innate and adaptive anti-bacterial immunity. Recently described soluble-CR forms can modulate immunity in inflammatory conditions, but the contributions of soluble-TIM3 and soluble-PD1 and other soluble-CRs to immune derangements in ALD remain unclear.In Alcoholic Hepatitis (AH; n = 19), alcohol-related cirrhosis (ARC; n = 53) and healthy control (HC; n = 27) subjects, we measured by Luminex technology (i) plasma levels of 16 soluble-CRs, 12 pro/anti-inflammatory cytokines and markers of gut bacterial translocation; (ii) pre-hepatic, post-hepatic and non-hepatic soluble-CR plasma levels in ARC patients undergoing TIPS; (iii) soluble-CRs production from ethanol-treated immunocompetent precision cut human liver slices (PCLS); (iv) whole-blood soluble-CR expression upon bacterial challenge. By FACS, we assessed the relationship between soluble-TIM3 and membrane-TIM3 and rescue of immunity in bacterial-challenged PBMCs.Soluble-TIM3 was the dominant plasma soluble-CR in ALD vs. HC (p = 0.00002) and multivariate analysis identified it as the main driver of differences between groups. Soluble-CRs were strongly correlated with pro-inflammatory cytokines, gut bacterial translocation markers and clinical indices of disease severity. Ethanol exposure or bacterial challenge did not induce soluble-TIM3 production from PCLS nor from whole-blood. Bacterial challenge prompted membrane-TIM3 hyperexpression on PBMCs from ALD patient's vs. HC (p < 0.002) and was inversely correlated with plasma soluble-TIM3 levels in matched patients. TIM3 ligands soluble-Galectin-9 and soluble-CEACAM1 were elevated in ALD plasma (AH > ARC; p < 0.002). In vitro neutralization of Galectin-9 and soluble-CEACAM1 improved the defective anti-bacterial and anti-inflammatory cytokine production from E. coli-challenged PBMCs in ALD patients.Alcohol-related liver disease patients exhibit supra-physiological plasma levels of soluble-TIM3, particularly those with greater disease severity. This is also associated with increased levels of soluble TIM3-ligands and membrane-TIM3 expression on immune cells. Soluble-TIM3 can block the TIM3-ligand synapse and improve anti-bacterial immunity; however, the increased levels of soluble TIM3-binding ligands in patients with ALD negate any potential immunostimulatory effects. We believe that anti-TIM3 neutralizing antibodies currently in Phase I clinical trials or soluble-TIM3 should be investigated further for their ability to enhance anti-bacterial immunity. These agents could potentially represent an innovative immune-based supportive approach to rescue anti-bacterial defenses in ALD patients." @default.
• W3134733355 created "2021-03-15" @default.
• W3134733355 creator A5002867454 @default.
• W3134733355 creator A5004044508 @default.
• W3134733355 creator A5017174323 @default.
• W3134733355 creator A5022608267 @default.
• W3134733355 creator A5029282864 @default.
• W3134733355 creator A5030477203 @default.
• W3134733355 creator A5030752242 @default.
• W3134733355 creator A5038002101 @default.
• W3134733355 creator A5038005360 @default.
• W3134733355 creator A5039978053 @default.
• W3134733355 creator A5040417146 @default.
• W3134733355 creator A5041300993 @default.
• W3134733355 creator A5041529320 @default.
• W3134733355 creator A5042891883 @default.
• W3134733355 creator A5052311858 @default.
• W3134733355 creator A5056621975 @default.
• W3134733355 creator A5056768920 @default.
• W3134733355 creator A5057399202 @default.
• W3134733355 creator A5058024088 @default.
• W3134733355 creator A5058675792 @default.
• W3134733355 creator A5069523379 @default.
• W3134733355 creator A5076160157 @default.
• W3134733355 creator A5081405161 @default.
• W3134733355 creator A5081837865 @default.
• W3134733355 creator A5086879562 @default.
• W3134733355 creator A5090432689 @default.
• W3134733355 date "2021-03-10" @default.
• W3134733355 modified "2023-10-17" @default.
• W3134733355 title "Soluble TIM3 and Its Ligands Galectin-9 and CEACAM1 Are in Disequilibrium During Alcohol-Related Liver Disease and Promote Impairment of Anti-bacterial Immunity" @default.
• W3134733355 cites W1543067125 @default.
• W3134733355 cites W1889183644 @default.
• W3134733355 cites W1920087348 @default.
• W3134733355 cites W1965999622 @default.
• W3134733355 cites W1966641879 @default.
• W3134733355 cites W1968113197 @default.
• W3134733355 cites W1968791512 @default.
• W3134733355 cites W1969972390 @default.
• W3134733355 cites W1976557086 @default.
• W3134733355 cites W1976800458 @default.
• W3134733355 cites W1978607785 @default.
• W3134733355 cites W1994015015 @default.
• W3134733355 cites W1998467778 @default.
• W3134733355 cites W1999411720 @default.
• W3134733355 cites W1999449285 @default.
• W3134733355 cites W2007435911 @default.
• W3134733355 cites W2009059990 @default.
• W3134733355 cites W2009616392 @default.
• W3134733355 cites W2012070966 @default.
• W3134733355 cites W2016318598 @default.
• W3134733355 cites W2028494898 @default.
• W3134733355 cites W2034568457 @default.
• W3134733355 cites W2040141151 @default.
• W3134733355 cites W2046828081 @default.
• W3134733355 cites W2059309195 @default.
• W3134733355 cites W2059714773 @default.
• W3134733355 cites W2060169824 @default.
• W3134733355 cites W2066193523 @default.
• W3134733355 cites W2070631889 @default.
• W3134733355 cites W2082203090 @default.
• W3134733355 cites W2085643863 @default.
• W3134733355 cites W2085964948 @default.
• W3134733355 cites W2091600198 @default.
• W3134733355 cites W2107777135 @default.
• W3134733355 cites W2108472443 @default.
• W3134733355 cites W2108565475 @default.
• W3134733355 cites W2119491144 @default.
• W3134733355 cites W2119503603 @default.
• W3134733355 cites W2121603793 @default.
• W3134733355 cites W2122730216 @default.
• W3134733355 cites W2124620436 @default.
• W3134733355 cites W2136919496 @default.
• W3134733355 cites W2141634817 @default.
• W3134733355 cites W2145428651 @default.
• W3134733355 cites W2145476394 @default.
• W3134733355 cites W2161929790 @default.
• W3134733355 cites W2162940124 @default.
• W3134733355 cites W2340708452 @default.
• W3134733355 cites W234547497 @default.
• W3134733355 cites W2519260049 @default.
• W3134733355 cites W2523691514 @default.
• W3134733355 cites W2561052156 @default.
• W3134733355 cites W2561573371 @default.
• W3134733355 cites W2593059553 @default.
• W3134733355 cites W2613286620 @default.
• W3134733355 cites W2618454703 @default.
• W3134733355 cites W2626452372 @default.
• W3134733355 cites W2735051780 @default.
• W3134733355 cites W2736267104 @default.
• W3134733355 cites W2738453388 @default.
• W3134733355 cites W2741699783 @default.
• W3134733355 cites W2761139137 @default.
• W3134733355 cites W2765152120 @default.
• W3134733355 cites W2770395397 @default.
• W3134733355 cites W2781839630 @default.
• W3134733355 cites W2795611455 @default.
• W3134733355 cites W2799958170 @default.
• W3134733355 cites W2801201298 @default.
• W3134733355 cites W2885677635 @default.

• next