1. Academic Validation
  2. Gut microbiota-mediated secondary bile acids regulate dendritic cells to attenuate autoimmune uveitis through TGR5 signaling

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

  • Cell Rep. 2021 Sep 21;36(12):109726. doi: 10.1016/j.celrep.2021.109726.
Jianping Hu 1 Chaokui Wang 1 Xinyue Huang 1 Shenglan Yi 1 Su Pan 1 Yiting Zhang 1 Gangxiang Yuan 1 Qingfeng Cao 1 Xingsheng Ye 1 Hong Li 2
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, P.R. China.
  • 2 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, P.R. China. Electronic address: lihongcqmu@163.com.
Abstract

Gut microbiota-mediated secondary bile acids (BAs) play an important role in energy balance and host metabolism via G protein-coupled receptors and/or nuclear receptors. Emerging evidence suggests that BAs are important for maintaining innate immune responses via these receptors. However, the effect of BAs on autoimmune uveitis is still unknown. Here, we demonstrate decreased microbiota-related secondary BA concentration in feces and serum of Animals with experimental autoimmune uveitis (EAU). Restoration of the gut BAs pool attenuates severity of EAU in association with inhibition of nuclear factor κB (NF-κB)-related pro-inflammatory cytokines in dendritic cells (DCs). TGR5 deficiency partially reverses the inhibitory effect of deoxycholic acid (DCA) on DCs. TGR5 signaling also inhibits NF-κB activation via the cyclic AMP (cAMP)-protein kinase A (PKA) pathway in DCs. Additionally, both DCA and TGR5 agonists inhibit human monocyte-derived DC activation. Taken together, our results suggest that BA metabolism plays an important role in adaptive immune responses and might be a therapeutic target in autoimmune uveitis.

Keywords

TGR5; autoimmune disease; bile acids; dendritic cells; uveitis.

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