2. Academic Validation
  3. Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice

Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice

  • Front Immunol. 2018 Sep 18;9:1984. doi: 10.3389/fimmu.2018.01984.
Sooghee Chang 1,  Youn-Hee Kim 1 2,  Young-Joo Kim 1 3,  Young-Woo Kim 2 3,  Sungyoon Moon 3,  Yong Yook Lee 3,  Jin Sun Jung 3,  Youngsoo Kim 2,  Hi-Eun Jung 2,  Tae-Joo Kim 2,  Taek-Chin Cheong 2,  Hye-Jung Moon 1,  Jung-Ah Cho 1 3,  Hang-Rae Kim 2 4,  Dohyun Han 5,  Yirang Na 1 5,  Seung-Hyeok Seok 1 5,  Nam-Hyuk Cho 1 2 3,  Hai-Chon Lee 3,  Eun-Hee Nam 3,  Hyosuk Cho 2,  Murim Choi 2,  Nagahiro Minato 6,  Seung-Yong Seong 1 2 3
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea.
  • 2 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
  • 3 Wide River Institute of Immunology, Seoul National University, Seoul, South Korea.
  • 4 Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea.
  • 5 Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
  • 6 Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
PMID: 30279688 DOI: 10.3389/fimmu.2018.01984
Abstract

Bile acids (BAs) control metabolism and inflammation by interacting with several receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA) decreases serum pro-inflammatory cytokines, normalizes hypotension, protects against renal injury, and prolongs mouse survival during sepsis. TDCA increases the number of granulocytic myeloid-derived suppressor cells (MDSCLT) distinctive from MDSCs obtained without TDCA treatment (MDSCL) in the spleen of septic mice. FACS-sorted MDSCLT cells suppress T-cell proliferation and confer protection against sepsis when adoptively transferred better than MDSCL. Proteogenomic analysis indicated that TDCA controls chromatin silencing, alternative splicing, and translation of the immune proteome of MDSCLT, which increases the expression of anti-inflammatory molecules such as oncostatin, lactoferrin and CD244. TDCA also decreases the expression of pro-inflammatory molecules such as neutrophil Elastase. These findings suggest that TDCA globally edits the proteome to increase the number of MDSCLT cells and affect their immune-regulatory functions to resolve systemic inflammation during sepsis.

Keywords

TGR5; inflammation; myeloid-derived suppressor cells; sepsis; taurodeoxycholate.

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