期刊
JCI INSIGHT
卷 5, 期 5, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.94035
关键词
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资金
- American Gastroenterological Association/Gastric Cancer Foundation [N017489]
- Department of Defense Peer Reviewed Cancer Research Program [CA160431]
- NIH [NIDDK R01 DK087708-01, 5P30DK034933]
Development of gastric cancer is often preceded by chronic inflammation, but the immune cellular mechanisms underlying this process are unclear. Here we demonstrated that an inflammasome molecule, absent in melanoma 2 (Aim2), was upregulated in patients with gastric cancer and in spasmolytic polypeptide-expressing metaplasia of chronically Helicobacter felis-infected stomachs in mice. However, we found that Aim2 was not necessary for inflammasome function during gastritis. In contrast, Aim2 deficiency led to an increase in gastric CD8(+) T cell frequency, which exacerbated metaplasia. These gastric CD8(+) T cells from Aim2(-/-) mice were found to have lost their homing receptor expression (sphingosinel-phosphate receptor 1 [S1PR1] and CD62L), a feature of tissue-resident memory T cells, The process was not mediated by Aim2-dependent regulation of IFN-beta or by dendritic cell-intrinsic Aim2. Rather, Aim2 deficiency contributed to an increased production of CXCL16 by B cells, which could suppress S1PR1 and CD62L in CD8(+) T cells. This study describes a potentially novel function of Aim2 that regulates CD8(+) T cell infiltration and retention within chronically inflamed solid organ tissue. This function operates independent of the inflammasome, IFN-beta, or dendritic cells. We provide evidence that B cells can contribute to this mechanism via CXCL16.
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