An Intestinal Th17 Subset is Associated with Inflammation in Crohn's Disease and Activated by Adherent-invasive Escherichia coli.

Autor: Paroni M; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Leccese G; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Ranzani V; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Moschetti G; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Chiara M; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Perillo F; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy., Ferri S; Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy., Clemente F; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Noviello D; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy., Conforti FS; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Ferrero S; Pathology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Biomedical, Surgical, and Dental Sciences, Università degli Studi di Milano, Milan, Italy., Karnani B; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Bosotti R; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Vasco C; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Curti S; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Crosti MC; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Gruarin P; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy., Rossetti G; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy.; Molecular Oncology and Immunology, FIRC Institute of Molecular Oncology [IFOM], Milan, Italy., Conte MP; Department of Public Health and Infectious Diseases, 'Sapienza' University of Rome, Rome, Italy., Vecchi M; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy., Pagani M; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy.; Molecular Oncology and Immunology, FIRC Institute of Molecular Oncology [IFOM], Milan, Italy.; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy., Landini P; Department of Biosciences, Università degli Studi di Milano, Milan, Italy., Facciotti F; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy.; Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.; Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy., Abrignani S; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy.; DISCCO, Department of Clinical Science and Community Health, University of Milan, Milan, Italy., Caprioli F; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy., Geginat J; INGM-National Institute of Molecular Genetics 'Romeo ed Enrica Invernizzi', Milan, Italy.; DISCCO, Department of Clinical Science and Community Health, University of Milan, Milan, Italy.
Jazyk: angličtina
Zdroj: Journal of Crohn's & colitis [J Crohns Colitis] 2023 Dec 30; Vol. 17 (12), pp. 1988-2001.
DOI: 10.1093/ecco-jcc/jjad119
Abstrakt: IFNγ-producing ex-Th17 cells ['Th1/17'] were shown to play a key pathogenic role in experimental colitis and are abundant in the intestine. Here, we identified and characterised a novel, potentially colitogenic subset of Th17 cells in the intestine of patients with Crohn's disease [CD]. Human Th17 cells expressing CCR5 ['pTh17'] co-expressed T-bet and RORC/γt and produced very high levels of IL-17, together with IFN-γ. They had a gene signature of Th17 effector cells and were distinct from established Th1/17 cells. pTh17 cells, but not Th1/17 cells, were associated with intestinal inflammation in CD, and decreased upon successful anti-TNF therapy with infliximab. Conventional CCR5[-]Th17 cells differentiated to pTh17 cells with IL-23 in vitro. Moreover, anti-IL-23 therapy with risankizumab strongly reduced pTh17 cells in the intestine. Importantly, intestinal pTh17 cells were selectively activated by adherent-invasive Escherichia coli [AIEC], but not by a commensal/probiotic E. coli strain. AIEC induced high levels of IL-23 and RANTES from dendritic cells [DC]. Intestinal CCR5+Th1/17 cells responded instead to cytomegalovirus and were reduced in ulcerative colitis [UC], suggesting an unexpected protective role. In conclusion, we identified an IL-23-inducible subset of human intestinal Th17 cells. pTh17 cells produced high levels of pro-inflammatory cytokines, were selectively associated with intestinal inflammation in CD, and responded to CD-associated AIEC, suggesting a key colitogenic role.
(© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
Databáze: MEDLINE
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