睁开全文精氨酸酶表达经由过程改变粪便菌群及代谢组以按捺肠道炎症减缓.JCI-, ArticleAbstract Authors:睁开Abstract:收起Arginase (Arg), which converts L-arginine into ornithine and urea, exerts pleiotropic immunoregulatory effects. However, the function of Arg in inflammatory bowel disease (IBD) remains poorly characterized. Here, we found that Arg expression correlated with the degree of inflammation in intestinal tissues from IBD patients. In mice, Arg was upregulated in an ILIL and intestinal microbiota-dependent manner. Tie-Cre -Argflfl mice lacking Arg in hematopoietic and endothelial cells recovered faster from experimental colitis than Arg-expressing littermates. This correlated with decreased vessel density, compositional changes in intestinal microbiota, diminished infiltration by myeloid cells and an accumulation of intraluminal polyamines that promote epithelial healing. The pro-resolving effect of Arg-deletion was reduced by an L-arginine-free diet, but rescued by simultaneous deletion of other L-arginine-metabolizing enzymes such as Arg or Nos, demonstrating that protection from colitis requires L-arginine. Fecal microbiota transfers from Tie-Cre -Argflfl mice into wild-type recipients ameliorated intestinal inflammation while transfers from wild-type littermates into Arg-deficient mice prevented an advanced recovery from colitis. Thus, an increased availability of L-arginine as well as altered intestinal microbiota and metabolic products account for the accelerated resolution from colitis in the absence of Arg. Consequently, the metaboli of L-arginine may serve as target for clinical intervention in IBD patients.First Authors:Julia Baier,Maximilian G?nauerCorrespondence Authors:Jochen MattnerAll Authors:Julia Baier,Maximilian G?nauer,Claudia Giessler,Harald Arnold,Mercedes Muske,Ulrike Schleicher,Soeren Lukassen,Arif B Ekici,Manfred Rauh,Christoph Daniel,Arndt Hartmann,Benjamin Schmid,Philipp Tripal,Katja Dettmer,Peter J Oefner,Raja Atreya,Stefan Wirtz,Christian Bogdan,Jochen Mattner