Macrophage Deficiency Makes Intestinal Epithelial Cells Susceptible to NSAID-Induced Damage

الملخص EN

Objectives.

In Crohn’s disease (CD), the mechanisms underlying the regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of mucosal barrier function in the ileum are unclear.

We analyzed the molecular mechanisms underlying the regulation by GM-CSF of the mucosal barrier function.

Methods.

We examined the role of GM-CSF in the intestinal barrier function in CD at the molecular-, cellular-, and animal-model levels.

Results.

Macrophages directly secreted GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis, which maintained intestinal barrier function.

Macrophages were absent in NSAID-induced ileitis, causing GM-CSF deficiency, increasing the apoptosis rate, decreasing the proliferation rate, increasing inter- and paracellular permeabilities, decreasing the TJP levels, and reducing the numbers of mesenteric lymph nodes, memory T cells, and regulatory T cells in Csf1op/op transgenic mice.

Conclusions.

GM-CSF is required for the maintenance of intestinal barrier function.

Macrophages directly secrete GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis.