| First Author | El-Zaatari M | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 5 | PubMed ID | 32053518 |
| Mgi Jnum | J:309360 | Mgi Id | MGI:6757570 |
| Doi | 10.1172/jci.insight.94035 | Citation | El-Zaatari M, et al. (2020) Aim2-mediated/IFN-beta-independent regulation of gastric metaplastic lesions via CD8+ T cells. JCI Insight 5(5) |
| abstractText | 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 (sphingosine-1-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. |
