Intestinal non-canonical NFκB signaling shapes the local and systemic immune response.
Animals
B-Lymphocytes
/ metabolism
Blotting, Western
Colitis
/ immunology
Colon
/ metabolism
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Humans
Immunoglobulin A
/ metabolism
Interleukin-17
/ metabolism
Intestines
/ immunology
Mice
NF-kappa B
/ metabolism
Protein Serine-Threonine Kinases
RNA, Ribosomal, 16S
/ genetics
Sepsis
/ genetics
Signal Transduction
/ physiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 02 2019
08 02 2019
Historique:
received:
20
05
2018
accepted:
21
01
2019
entrez:
10
2
2019
pubmed:
10
2
2019
medline:
9
4
2019
Statut:
epublish
Résumé
Microfold cells (M-cells) are specialized cells of the intestine that sample luminal microbiota and dietary antigens to educate the immune cells of the intestinal lymphoid follicles. The function of M-cells in systemic inflammatory responses are still unclear. Here we show that epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase (NIK) is highly active in intestinal lymphoid follicles, and is required for M-cell maintenance. Intestinal NIK signaling modulates M-cell differentiation and elicits both local and systemic IL-17A and IgA production. Importantly, intestinal NIK signaling is active in mouse models of colitis and patients with inflammatory bowel diseases; meanwhile, constitutive NIK signaling increases the susceptibility to inflammatory injury by inducing ectopic M-cell differentiation and a chronic increase of IL-17A. Our work thus defines an important function of non-canonical NFkB and M-cells in immune homeostasis, inflammation and polymicrobial sepsis.
Identifiants
pubmed: 30737385
doi: 10.1038/s41467-019-08581-8
pii: 10.1038/s41467-019-08581-8
pmc: PMC6368617
doi:
Substances chimiques
Immunoglobulin A
0
Interleukin-17
0
NF-kappa B
0
RNA, Ribosomal, 16S
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
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
660Subventions
Organisme : NIDDK NIH HHS
ID : K99 DK110537
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA148828
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK091591
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK114376
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046592
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007517
Pays : United States
Organisme : NIDDK NIH HHS
ID : F31 DK116555
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008322
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034933
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK095782
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK094775
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007315
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK095201
Pays : United States
Organisme : NIDDK NIH HHS
ID : R00 DK110537
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES028802
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA130810
Pays : United States
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