RRC ID 65991
Author Lina TT, Pinchuk IV, House J, Yamaoka Y, Graham DY, Beswick EJ, Reyes VE.
Title CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection.
Journal J Immunol
Abstract Gastric epithelial cells (GECs) are the primary target for Helicobacter pylori infection and may act as APCs regulating local T cell responses. We previously reported that H. pylori infection of GECs induces the expression of the T cell coinhibitory molecule B7-H1 on GECs. This process contributes to the hyporesponsiveness of CD4(+) effector T cells and accumulation of regulatory T cells. In the present study, we investigated the impact of H. pylori cytotoxin-associated gene A (CagA) on the modulation of the expression of the T cell costimulator B7-H2 by GECs. B7-H2 is involved in promoting Th17 type responses. H. pylori infection downregulates B7-H2 expression by GECs in a CagA-dependent manner. IFN-γ, which is increased in the H. pylori-infected gastric mucosa, synergizes with H. pylori in downregulating B7-H2 expression by GECs. CagA-mediated modulation of B7-H2 on GECs involves p70 S6 kinase phosphorylation. The CagA-dependent B7-H2 downregulation in GECs correlates with a decrease in Th17 type responses in vitro and in vivo. Furthermore, CagA-dependent modulation of Th17 responses was inversely correlated with the H. pylori colonization levels in vivo. Our data suggest that CagA contributes to the ability of H. pylori to evade Th17-mediated clearance by modulating expression of B7-H2 and, thus, to the establishment of the H. pylori chronic infection.
Volume 191(7)
Pages 3838-46
Published 2013-10-1
DOI 10.4049/jimmunol.1300524
PII jimmunol.1300524
PMID 23997227
PMC PMC3801271
MeSH Animals Antigens, Bacterial / metabolism* Bacterial Proteins / metabolism* Cell Line Down-Regulation Female Gastric Mucosa / immunology* Gastric Mucosa / microbiology* Gene Expression Regulation / drug effects Helicobacter Infections / immunology* Helicobacter pylori / metabolism* Humans Inducible T-Cell Co-Stimulator Ligand / genetics* Inducible T-Cell Co-Stimulator Ligand / metabolism Interferon-gamma / pharmacology Mice Ribosomal Protein S6 Kinases, 70-kDa / metabolism TOR Serine-Threonine Kinases / metabolism Th17 Cells / immunology* Th17 Cells / metabolism*
IF 4.886
Human and Animal Cells HGC-27(RCB0500)