Group 3 innate lymphoid cells produce the growth factor HB-EGF to protect the intestine from TNF-mediated inflammation.

Animals Epithelial Cells / immunology Heparin-binding EGF-like Growth Factor / immunology Immunity, Innate / immunology Inflammation / immunology Intestinal Mucosa / immunology Intestines / immunology Lymphocytes / immunology Mice Mice, Inbred C57BL Signal Transduction / immunology Tumor Necrosis Factor-alpha / immunology

Journal

Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354

Informations de publication

Date de publication:
02 2022
Historique:
received: 01 04 2021
accepted: 02 12 2021
pubmed: 2 2 2022
medline: 19 2 2022
entrez: 1 2 2022
Statut: ppublish

Résumé

Tumor necrosis factor (TNF) drives chronic inflammation and cell death in the intestine, and blocking TNF is a therapeutic approach in inflammatory bowel disease (IBD). Despite this knowledge, the pathways that protect the intestine from TNF are incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3s) protect the intestinal epithelium from TNF-induced cell death. This occurs independent of interleukin-22 (IL-22), and we identify that ILC3s are a dominant source of heparin-binding epidermal growth factor-like growth factor (HB-EGF). ILC3s produce HB-EGF in response to prostaglandin E2 (PGE2) and engagement of the EP2 receptor. Mice lacking ILC3-derived HB-EGF exhibit increased susceptibility to TNF-mediated epithelial cell death and experimental intestinal inflammation. Finally, human ILC3s produce HB-EGF and are reduced from the inflamed intestine. These results define an essential role for ILC3-derived HB-EGF in protecting the intestine from TNF and indicate that disruption of this pathway contributes to IBD.

Identifiants

DOI: 10.1038/s41590-021-01110-0 PMID: 35102343 PMC: PMC8842850
pubmed: 35102343
doi: 10.1038/s41590-021-01110-0
pii: 10.1038/s41590-021-01110-0
pmc: PMC8842850
mid: NIHMS1768023
doi:

Substances chimiques

Hbegf protein, mouse 0
Heparin-binding EGF-like Growth Factor 0
Tumor Necrosis Factor-alpha 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

251-261

Subventions

Organisme : NIDDK NIH HHS
ID : T32 DK116970
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI142213
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI162936
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA249274
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145989
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI123368
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126871
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143842
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI095608
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Lei Zhou (L)

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA. lez2004@med.cornell.edu.
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA. lez2004@med.cornell.edu.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA. lez2004@med.cornell.edu.
ORCID: 0000-0002-7454-3070

Wenqing Zhou (W)

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA.
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0002-8800-3745

Ann M Joseph (AM)

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA.
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.

Coco Chu (C)

Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.

Gregory G Putzel (GG)

Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.

Beibei Fang (B)

Immunology and Microbial Pathogenesis Program, Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY, USA.

Fei Teng (F)

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA.
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.

Mengze Lyu (M)

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA.
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0002-8509-7969

Hiroshi Yano (H)

Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0002-3098-2629

Katrin I Andreasson (KI)

Department of Neurology & Neurological Sciences, Stanford Neuroscience Institute, Stanford Immunology Program, Stanford School of Medicine, Stanford, CA, USA.
ORCID: 0000-0001-8391-4155

Eisuke Mekada (E)

Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
ORCID: 0000-0001-8858-4781

Gerard Eberl (G)

Microenvironment and Immunity Unit, Institut Pasteur, Paris, France.
ORCID: 0000-0002-1119-5638

Gregory F Sonnenberg (GF)

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, NY, USA. gfsonnenberg@med.cornell.edu.
Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA. gfsonnenberg@med.cornell.edu.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA. gfsonnenberg@med.cornell.edu.
ORCID: 0000-0003-0948-5908

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Cellules › Cellules épithéliales › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la famille de l'EGF › Facteur de croissance de type EGF liant l'héparine › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse intestinale › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Système digestif › Tube digestif › Intestins › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Group 3 innate lymphoid cells produce the...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Group 3 innate lymphoid cells produce the...