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Arginase impedes the resolution of colitis by altering the microbiome and metabolome.
Baier, Julia; Gänsbauer, Maximilian; Giessler, Claudia; Arnold, Harald; Muske, Mercedes; Schleicher, Ulrike; Lukassen, Sören; Ekici, Arif; Rauh, Manfred; Daniel, Christoph; Hartmann, Arndt; Schmid, Benjamin; Tripal, Philipp; Dettmer, Katja; Oefner, Peter J; Atreya, Raja; Wirtz, Stefan; Bogdan, Christian; Mattner, Jochen.
Afiliação
  • Baier J; Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie und Hygiene.
  • Gänsbauer M; Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie und Hygiene.
  • Giessler C; Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie und Hygiene.
  • Arnold H; Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie und Hygiene.
  • Muske M; Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie und Hygiene.
  • Schleicher U; Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie und Hygiene.
  • Lukassen S; Humangenetisches Institut.
  • Ekici A; Humangenetisches Institut.
  • Rauh M; Kinder- und Jugendklinik.
  • Daniel C; Nephropathologische Abteilung, and.
  • Hartmann A; Pathologisches Institut, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
  • Schmid B; Optical Imaging Centre Erlangen (OICE), FAU Erlangen-Nürnberg, Erlangen, Germany.
  • Tripal P; Optical Imaging Centre Erlangen (OICE), FAU Erlangen-Nürnberg, Erlangen, Germany.
  • Dettmer K; Institut für Funktionelle Genomik, Universität Regensburg, Regensburg, Germany.
  • Oefner PJ; Institut für Funktionelle Genomik, Universität Regensburg, Regensburg, Germany.
  • Atreya R; Medizinische Klinik 1-Gastroenterologie, Pneumologie and Endokrinologie, Universitätsklinikum Erlangen and FAU Erlangen-Nürnberg, Erlangen, Germany.
  • Wirtz S; Medizinische Klinik 1-Gastroenterologie, Pneumologie and Endokrinologie, Universitätsklinikum Erlangen and FAU Erlangen-Nürnberg, Erlangen, Germany.
  • Bogdan C; Medical Immunology Campus Erlangen, FAU Erlangen-Nürnberg, Erlangen, Germany.
  • Mattner J; Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie und Hygiene.
J Clin Invest ; 130(11): 5703-5720, 2020 11 02.
Article em En | MEDLINE | ID: mdl-32721946
Arginase 1 (Arg1), which converts l-arginine into ornithine and urea, exerts pleiotropic immunoregulatory effects. However, the function of Arg1 in inflammatory bowel disease (IBD) remains poorly characterized. Here, we found that Arg1 expression correlated with the degree of inflammation in intestinal tissues from IBD patients. In mice, Arg1 was upregulated in an IL-4/IL-13- and intestinal microbiota-dependent manner. Tie2-Cre Arg1fl/fl mice lacking Arg1 in hematopoietic and endothelial cells recovered faster from colitis than Arg1-expressing (Arg1fl/fl) 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 proresolving effect of Arg1 deletion was reduced by an l-arginine-free diet, but rescued by simultaneous deletion of other l-arginine-metabolizing enzymes, such as Arg2 or Nos2, demonstrating that protection from colitis requires l-arginine. Fecal microbiota transfers from Tie2-Cre Arg1fl/fl mice into WT recipients ameliorated intestinal inflammation, while transfers from WT littermates into Arg1-deficient mice prevented an advanced recovery from colitis. Thus, an increased availability of l-arginine as well as altered intestinal microbiota and metabolic products accounts for the accelerated resolution from colitis in the absence of Arg1. Consequently, l-arginine metabolism may serve as a target for clinical intervention in IBD patients.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arginase / Doenças Inflamatórias Intestinais / Hiperargininemia / Metaboloma / Microbioma Gastrointestinal Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arginase / Doenças Inflamatórias Intestinais / Hiperargininemia / Metaboloma / Microbioma Gastrointestinal Idioma: En Ano de publicação: 2020 Tipo de documento: Article