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mTOR-Myc axis drives acinar-to-dendritic cell transition and the CD4(+) T cell immune response in acute pancreatitis
The inflammatory response in acute pancreatitis (AP) is associated with acinar-to-dendritic cell transition. The CD4(+) T-cell-mediated adaptive immune response is necessary for pancreatic inflammatory damage. However, the effect of acinar-to-dendritic cell transition on the CD4(+) T-cell response a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265283/ https://www.ncbi.nlm.nih.gov/pubmed/32488108 http://dx.doi.org/10.1038/s41419-020-2517-x |
Sumario: | The inflammatory response in acute pancreatitis (AP) is associated with acinar-to-dendritic cell transition. The CD4(+) T-cell-mediated adaptive immune response is necessary for pancreatic inflammatory damage. However, the effect of acinar-to-dendritic cell transition on the CD4(+) T-cell response and the regulatory mechanism remain undefined. A mouse animal model of AP was established by repeated intraperitoneal injection of CAE. The mTOR inhibitor rapamycin was administered before AP induction. Primary acinar cells were isolated and co-incubated with subsets of differentiated CD4(+) T cells. The expression of DC-SIGN was also assessed in pancreatic tissues from human AP patients. We found acinar cells expressed DC-SIGN and displayed the phenotype of dendritic cells (DCs), which promoted the differentiation of naive CD4(+) T cells into CD4(+)/IFN-γ(+) Th1 and CD4(+)/IL-17A(+) Th17 cells in pancreatic tissues during AP. DC-SIGN was the target gene of Myc. The mTOR inhibitor rapamycin inhibited AP-induced DC-SIGN expression, CD4(+) Th1/Th17 cell differentiation and the pro-inflammatory response via Myc. Acinar cells expressed DC-SIGN in pancreatic tissues of human patients with AP. In conclusion, acinar-to-dendritic cell transition is implicated in the CD4(+) T-cell immune response via mTOR-Myc-DC-SIGN axis, which might be an effective target for the prevention of local pancreatic inflammation in AP. |
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