Decreased Expression of TGR5 in Vogt-Koyanagi-Harada (VKH) Disease

Gut microbiota-mediated secondary bile acids regulate dendritic cells to attenuate autoimmune uveitis through TGR5 signaling

“…To verify whether our findings in animals can be extrapolated to humans, we selected two types of clinical uveitis, namely VKH disease and BD, representing an autoimmune disease and an autoinflammatory disease, respectively. In line with our previous study demonstrating decreased TGR5 expression on macrophages in active VKH disease patients (Yang et al, 2020), we herein demonstrated a decreased expression of TGR5 on DCs in both active BD and active VKH disease patients. INT-777 and DCA both inhibited pro-inflammatory cytokine and surface marker expression in Mo-DCs from BD and VKH disease patients in association with a decreased NF-kB activation.…”

“…Gut microbiota and their metabolites have been implicated as potential modulators of the immune response in inflammatory and autoimmune diseases, including autoimmune uveitis (Huang et al, 2018a;Kalyana Chakravarthy et al, 2018;Maukonen et al, 2015;Nakamura et al, 2016;Stoll et al, 2014;Tremlett et al, 2016;Ye et al, 2018Ye et al, , 2020. Our current study revealed a decreased level of Ruminococcaceae and Lachnospiraceae in EAU mouse feces, the two of which have been previously identified to be decreased in various autoimmune diseases such as inflammatory bowel disease (Maukonen et al, 2015), pediatric multiple sclerosis (Tremlett et al, 2016), inflammatory uveitis (Kalyana Chakravarthy et al, 2018), enthesitis-related arthritis (Stoll et al, 2014), and type 1 diabetes (Candon et al, 2015).…”

“…There are many species of bacteria in the gut that have been shown to be involved in bile acid metabolism, especially the species that belong to Clostridium (Fiorucci et al, 2018). Although, Clostridium was not found by 16S rDNA sequencing in the gut of EAU or healthy mice; however, C. scindens was observed to have decreased in the feces of EAU mice in this study, and it was shown to have been depleted in BD, VKH disease, and AAU patients (Huang et al, 2018a;Ye et al, 2018Ye et al, , 2020. C. scindens has been shown to successfully help rebuild a healthy bile acid metabolism in mice (Ma et al, 2018;Winkler et al, 2020).…”

“…Recent studies showed that dysbiosis of the gut microbiome might play an important role in modulating immune homeostasis in clinical uveitis entities such as Behç et's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and acute anterior uveitis (AAU), but also in a model of experimental autoimmune uveitis (EAU) (Huang et al, 2018a;Janowitz et al, 2019;Ye et al, 2018Ye et al, , 2020. Transplantation of feces from clinically active BD uveitis patients to mice was shown to worsen EAU in these animals (Ye et al, 2018).…”

TGR5 deficiency activates antitumor immunity in non-small cell lung cancer via restraining M2 macrophage polarization

“…TGR5 is expressed in macrophages and TGR5 agonist attenuates inflammation factor release in atherosclerosis 16 , experimental autoimmune encephalomyelitis 17 and inflammatory bowel diseases 18 , 19 . Besides, TGR5 activation in macrophages co-cultured with CD4 + T cells inhibited Th1 and Th17 polarization in Vogt-Koyanagi-Harada disease 20 . All these indicated that TGR5 in macrophage plays a role in regulating inflammatory response.…”