AUTHOR=Chang Sooghee , Kim Youn-Hee , Kim Young-Joo , Kim Young-Woo , Moon Sungyoon , Lee Yong Yook , Jung Jin Sun , Kim Youngsoo , Jung Hi-Eun , Kim Tae-Joo , Cheong Taek-Chin , Moon Hye-Jung , Cho Jung-Ah , Kim Hang-Rae , Han Dohyun , Na Yirang , Seok Seung-Hyeok , Cho Nam-Hyuk , Lee Hai-Chon , Nam Eun-Hee , Cho Hyosuk , Choi Murim , Minato Nagahiro , Seong Seung-Yong TITLE=Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01984 DOI=10.3389/fimmu.2018.01984 ISSN=1664-3224 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.