Inhibiting PGGT1B Disrupts Function of RHOA, Resulting in T-cell Expression of Integrin α4β7 and Development of Colitis in Mice.
Adaptive Immunity
Alkyl and Aryl Transferases
/ deficiency
Animals
Case-Control Studies
Cells, Cultured
Chemotaxis, Leukocyte
Colitis
/ enzymology
Colon
/ enzymology
Cytokines
/ metabolism
Disease Models, Animal
Homeodomain Proteins
/ genetics
Humans
Immunity, Innate
Inflammation Mediators
/ metabolism
Integrins
/ metabolism
Lymphocyte Activation
Mice, Knockout
Neuropeptides
/ genetics
Signal Transduction
T-Lymphocytes
/ enzymology
cdc42 GTP-Binding Protein
/ genetics
rac1 GTP-Binding Protein
/ genetics
rho GTP-Binding Proteins
/ deficiency
rhoA GTP-Binding Protein
IBD
Immune Regulation
Mouse Models
Prenylation
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
23
08
2018
revised:
01
07
2019
accepted:
07
07
2019
pubmed:
16
7
2019
medline:
20
12
2019
entrez:
15
7
2019
Statut:
ppublish
Résumé
It is not clear how regulation of T-cell function is altered during development of inflammatory bowel diseases (IBD). We studied the mechanisms by which geranylgeranyltransferase-mediated prenylation controls T-cell localization to the intestine and chronic inflammation. We generated mice with T-cell-specific disruption of the geranylgeranyltransferase type I, beta subunit gene (Pggt1b), called Pggt1b Pggt1b Loss of PGGT1B from T cells in mice impairs RHOA function, increasing CD4+ T-cell expression of integrin alpha4beta7 and localization to colon, resulting in increased expression of inflammatory cytokines and colitis. T cells isolated from gut tissues from patients with IBD have lower levels of PGGT1B than tissues from patients without IBD.
Sections du résumé
BACKGROUND & AIMS
It is not clear how regulation of T-cell function is altered during development of inflammatory bowel diseases (IBD). We studied the mechanisms by which geranylgeranyltransferase-mediated prenylation controls T-cell localization to the intestine and chronic inflammation.
METHODS
We generated mice with T-cell-specific disruption of the geranylgeranyltransferase type I, beta subunit gene (Pggt1b), called Pggt1b
RESULTS
Pggt1b
CONCLUSION
Loss of PGGT1B from T cells in mice impairs RHOA function, increasing CD4+ T-cell expression of integrin alpha4beta7 and localization to colon, resulting in increased expression of inflammatory cytokines and colitis. T cells isolated from gut tissues from patients with IBD have lower levels of PGGT1B than tissues from patients without IBD.
Identifiants
pubmed: 31302143
pii: S0016-5085(19)41087-1
doi: 10.1053/j.gastro.2019.07.007
pii:
doi:
Substances chimiques
Cdc42 protein, mouse
0
Cytokines
0
Homeodomain Proteins
0
Inflammation Mediators
0
Integrins
0
Neuropeptides
0
Rac1 protein, mouse
0
integrin alpha4beta7
0
RAG-1 protein
128559-51-3
Alkyl and Aryl Transferases
EC 2.5.-
geranylgeranyltransferase type-I
EC 2.5.1.-
RhoA protein, mouse
EC 3.6.5.2
cdc42 GTP-Binding Protein
EC 3.6.5.2
rac1 GTP-Binding Protein
EC 3.6.5.2
rho GTP-Binding Proteins
EC 3.6.5.2
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1293-1309Informations de copyright
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.