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Updated: Dec 28, 2025
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Aim2-mediated/IFN-β-independent regulation of gastric metaplastic lesions via CD8+ T cells
Mohamad El-Zaatari1, Shrinivas Bishu1, Min Zhang1
1Division of Gastroenterology and Hepatology, Department of Internal Medicine.
Abstract:
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-β 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-β, or dendritic cells. We provide evidence that B cells can contribute to this mechanism via CXCL16.
Insights
Absent in melanoma 2 (Aim2) regulates gastric CD8+ T cells, independent of inflammasome activity. Aim2 deficiency increases gastric CD8+ T cells, exacerbating metaplasia via B cell CXCL16 production.
Area of Science:
- Immunology
- Gastroenterology
- Oncology
Background:
- Gastric cancer development is linked to chronic inflammation, but underlying immune mechanisms remain unclear.
- The inflammasome molecule absent in melanoma 2 (Aim2) is upregulated in gastric cancer patients and mouse models.
- The precise role of Aim2 in gastric inflammation and cancer progression is not fully understood.
Purpose of the Study:
- To investigate the role of Aim2 in the immune cellular mechanisms of chronic gastritis and gastric metaplasia.
- To determine if Aim2 influences CD8+ T cell behavior and infiltration in the gastric tissue.
- To elucidate the signaling pathways and cell types involved in Aim2-mediated regulation of gastric inflammation.
Main Methods:
- Analysis of Aim2 expression in human gastric cancer tissues and a mouse model of chronic Helicobacter felis infection.
- Assessment of gastric CD8+ T cell frequency and phenotype in Aim2-deficient (Aim2-/-) and wild-type mice.
- Investigation of homing receptor expression (S1PR1, CD62L) on CD8+ T cells.
- Evaluation of the role of IFN-β, dendritic cells, and B cell-derived CXCL16 in the observed phenotypes.
Main Results:
- Aim2 was upregulated in gastric cancer and chronic gastritis models but not essential for inflammasome function.
- Aim2 deficiency resulted in increased gastric CD8+ T cell frequency, exacerbating metaplasia.
- CD8+ T cells in Aim2-/- mice showed reduced expression of homing receptors (S1PR1, CD62L), characteristic of tissue-resident memory T cells.
- This effect was independent of Aim2-dependent IFN-β or dendritic cells, but linked to increased B cell production of CXCL16, which suppressed CD8+ T cell homing receptors.
Conclusions:
- Aim2 plays a novel, inflammasome-independent role in regulating CD8+ T cell infiltration and retention in chronically inflamed gastric tissue.
- B cell-derived CXCL16 mediates the suppressive effect of Aim2 deficiency on CD8+ T cell homing.
- These findings reveal a new mechanism by which Aim2 influences gastric immune responses and potentially cancer development.
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