The enteric nervous system relays psychological stress to intestinal inflammation.

Humans Glucocorticoids / pharmacology Inflammation Enteric Nervous System / physiology Inflammatory Bowel Diseases Stress, Psychological
IBD enteric glia enteric nervous system enteric neurons glucocorticoids monocytes neuro-immune interactions psychological stress

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
22 06 2023
Historique:
received: 28 07 2022
revised: 12 04 2023
accepted: 02 05 2023
pmc-release: 22 06 2024
medline: 26 6 2023
pubmed: 27 5 2023
entrez: 26 5 2023
Statut: ppublish

Résumé

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-β2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.

Identifiants

DOI: 10.1016/j.cell.2023.05.001 PMID: 37236193 PMC: PMC10330875
pubmed: 37236193
pii: S0092-8674(23)00475-0
doi: 10.1016/j.cell.2023.05.001
pmc: PMC10330875
mid: NIHMS1905077
pii:
doi:

Substances chimiques

Glucocorticoids 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2823-2838.e20

Subventions

Organisme : NCI NIH HHS
ID : P01 CA210944
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122798
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL160065
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155577
Pays : United States
Organisme : NIA NIH HHS
ID : DP2 AG067511
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI082630
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI115712
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK129691
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128282
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK019525
Pays : United States
Organisme : NIA NIH HHS
ID : DP2 AG067492
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI141393
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK050306
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117950
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS116574
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI108545
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests E.J.W. is an advisor for Danger Bio, Janssen, New Limit, Marengo, Pluto Immunotherapeutics Related Sciences, Rubius Therapeutics, Santa Ana Bio, Synthekine, and Surface Oncology. E.J.W. is a founder of and holds stock in Surface Oncology, Danger Bio, and Arsenal Biosciences.

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Auteurs

Kai Markus Schneider (KM)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Niklas Blank (N)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.

Yelina Alvarez (Y)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Katharina Thum (K)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Patrick Lundgren (P)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Lev Litichevskiy (L)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Madeleine Sleeman (M)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Klaas Bahnsen (K)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Jihee Kim (J)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Simon Kardo (S)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Shaan Patel (S)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Lenka Dohnalová (L)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Giulia T Uhr (GT)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Hélène C Descamps (HC)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Susanna Kircher (S)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Alana M McSween (AM)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Ashkan Rezazadeh Ardabili (AR)

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.

Kelsey M Nemec (KM)

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Monica T Jimenez (MT)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Lila G Glotfelty (LG)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Joshua D Eisenberg (JD)

Department of Pediatrics, Children's Hospital of Philadelphia Research Institute, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Emma E Furth (EE)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Jorge Henao-Mejia (J)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Pennsylvania, University of Pennsylvania, Philadelphia, PA 19104, USA.

F Chris Bennett (FC)

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Marie J Pierik (MJ)

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.

Mariëlle Romberg-Camps (M)

Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Centre, Sittard-Geleen, the Netherlands.

Zlatan Mujagic (Z)

Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands; School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands.

Marco Prinz (M)

Institute of Neuropathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany; Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Carolin V Schneider (CV)

Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

E John Wherry (EJ)

Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Meenakshi Bewtra (M)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Robert O Heuckeroth (RO)

Department of Pediatrics, Children's Hospital of Philadelphia Research Institute, and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Maayan Levy (M)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: maayanle@pennmedicine.upenn.edu.

Christoph A Thaiss (CA)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: thaiss@pennmedicine.upenn.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The enteric nervous system relays...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Hormones › Glucocorticoïdes › The enteric nervous system relays...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › The enteric nervous system relays...
questionsmedicales.fr › Système nerveux › Système nerveux périphérique › Système nerveux autonome › Système nerveux entérique › The enteric nervous system relays...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies inflammatoires intestinales › The enteric nervous system relays...
questionsmedicales.fr › Phénomènes psychologiques › Stress psychologique › The enteric nervous system relays...