CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection.
CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection.
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DOI：
10.4049/jimmunol.1300524
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发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Reyes VE
中科院分区：
文献类型：
--
作者：
Lina TT;Pinchuk IV;House J;Yamaoka Y;Graham DY;Beswick EJ;Reyes VE
胃上皮细胞（GECs）是幽门螺杆菌（H. pylori）感染，并可作为抗原呈递细胞（APC）调节局部T细胞应答。我们以前报道过H.幽门螺杆菌感染GEC诱导GEC上T细胞共抑制分子B7-H1的表达。这一过程有助于CD 4+效应T细胞的低反应性和调节性T细胞的积累。在本研究中，我们调查了H。pylori细胞毒素CagA对GEC调节T细胞共刺激分子B7-H2表达的影响。B7-H2参与促进Th 17型应答。H. pylori感染以CagA依赖性方式下调GECs的B7-H2表达。IFNγ在H. pylori感染的胃粘膜，与H. pylori下调GECs B7-H2表达。CagA介导的B7-H2对GEC的调节涉及p70 S6激酶磷酸化。GEC中CagA依赖的B7-H2下调与体外和体内Th 17型应答的减少相关。此外，CagA依赖性调节Th 17反应与H.体内幽门螺杆菌定植水平。我们的数据表明，CagA有助于H。pylori通过调节B7-H2的表达来逃避Th 17介导的清除，从而建立H.幽门螺杆菌慢性感染。
Gastric epithelial cells (GECs) are the primary target for Helicobacter pylori (H. pylori) infection and may act as antigen presenting cells (APC) regulating local T cell responses. We previously reported that H. pylori infection of GECs induces the expression of the T cell co-inhibitory molecule B7-H1 on GECs. This process contributes to the hyporesponsiveness of CD4+ effector T cells and accumulation of T regulatory cells. In the studies presented herein we investigated the impact of H. pylori cytotoxin CagA on the modulation of the expression of the T cell co-stimulator B7-H2 by GEC. B7-H2 is involved in promoting Th17 type responses. H. pylori infection downregulates B7-H2 expression by GECs in a CagA dependent manner. IFNγ, 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 GEC involves p70 S6 kinase phosphorylation. The CagA-dependent B7-H2 downregulation in GEC correlates with a decrease in Th17 type responses in vitro and in vivo. Further, CagA-dependent modulation of Th17 responses 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.
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影响因子：
29.4
作者：
DeLyria ES;Redline RW;Blanchard TG
通讯作者：
Blanchard TG
DOI：
10.1007/s004380050677
发表时间：
1998-03-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
Heuermann, D;Haas, R
通讯作者：
Haas, R
影响因子：
29.4
作者：
Huang, JQ;Sridhar, S;Hunt, RH
通讯作者：
Hunt, RH
影响因子：
3.1
作者：
Beswick, Ellen J.;Pinchuk, Irina V.;Reyes, Victor E.
通讯作者：
Reyes, Victor E.
影响因子：
29.4
作者：
CROWE, SE;ALVAREZ, L;ERNST, PB
通讯作者：
ERNST, PB