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=Volume 9 - 2018

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 (MDSC-LT) distinctive from MDSCs obtained without TDCA treatment (MDSC-L) in the spleen of septic mice. FACS-sorted MDSC-LT cells suppress T-cell proliferation and confer protection against sepsis when adoptively transferred better than MDSC-L. Proteogenomic analysis indicated that TDCA controls chromatin silencing, alternative splicing, and translation of the immune proteome of MDSC-LT, 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.