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10.1038/s41418-017-0006-2

http://scihub22266oqcxt.onion/10.1038/s41418-017-0006-2
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C6030103!6030103!29238069
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suck abstract from ncbi


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pmid29238069      Cell+Death+Differ 2018 ; 25 (7): 1209-23
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  • Kynurenic acid, an IDO metabolite, controls TSG-6-mediated immunosuppression of human mesenchymal stem cells #MMPMID29238069
  • Wang G; Cao K; Liu K; Xue Y; Roberts AI; Li F; Han Y; Rabson AB; Wang Y; Shi Y
  • Cell Death Differ 2018[Jul]; 25 (7): 1209-23 PMID29238069show ga
  • Mesenchymal stem cells (MSCs) have been demonstrated to be anti-inflammatory against various immune disorders through several factors, including indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene 6 (TSG-6). However, little is known about the necessity for both of these key immunosuppressive factors. Here we employed the mouse lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and found that IDO is necessary to achieve the effect of human umbilical cord-derived MSC (hUC-MSC)-based treatment on ALI. Notably, when IDO was deleted or inhibited, the expression of TSG-6 was decreased. This specific IDO-mediated regulation of TSG-6 expression was found to be exerted through its metabolite, kynurenic acid (KYNA), as inhibition of KYNA production led to decreased TSG-6 expression. Importantly, KYNA pretreatment of human MSCs enhanced their therapeutic effect on ALI. Mechanistically, KYNA activates aryl hydrocarbon receptor (AhR), which directly binds to the TSG-6 promoter to enhance TSG-6 expression. Therefore, our study has uncovered a novel link between IDO and TSG-6, and demonstrates that a metabolite of IDO controls the TSG-6-mediated anti-inflammatory therapeutic effects of human MSCs.
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