Park, H.-S.; Choi, S.; Back, Y.-W.; Lee, K.-I.; Choi, H.-G.; Kim, H.-J. Mycobacterium tuberculosis RpfE-Induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation. Int. J. Mol. Sci.2021, 22, 7535.
Park, H.-S.; Choi, S.; Back, Y.-W.; Lee, K.-I.; Choi, H.-G.; Kim, H.-J. Mycobacterium tuberculosis RpfE-Induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation. Int. J. Mol. Sci. 2021, 22, 7535.
Park, H.-S.; Choi, S.; Back, Y.-W.; Lee, K.-I.; Choi, H.-G.; Kim, H.-J. Mycobacterium tuberculosis RpfE-Induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation. Int. J. Mol. Sci.2021, 22, 7535.
Park, H.-S.; Choi, S.; Back, Y.-W.; Lee, K.-I.; Choi, H.-G.; Kim, H.-J. Mycobacterium tuberculosis RpfE-Induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation. Int. J. Mol. Sci. 2021, 22, 7535.
Abstract
Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Currently, there are no reports on the mycobacterial components that regulate PGE2 production. Previously, we have reported that RpfE-treated dendritic cells (DCs) effectively expanded the Th1 and Th17 cell responses simultaneously; however, the mechanism underlying Th1 and Th17 cell differentiation is unclear. Here, we show that PGE2 produced by RpfE-activated DCs via the MAPK and cyclooxygenase 2 signaling pathways induces Th1 and Th17 cell responses mainly via the EP4 receptor. Furthermore, mice administered intranasally with PGE2 displayed RpfE-induced antigen-specific Th1 and Th17 responses with a significant reduction in bacterial load in the lungs. Furthermore, the addition of optimal PGE2 amount to IL-2-IL-6-IL-23p19-IL-1β was essential for promoting differentiation into Th1/Th17 cells with strong bactericidal activity. These results suggest that RpfE-matured DCs produce PGE2 that induces Th1 and Th17 cell differentiation with potent anti-mycobacterial activity.
Keywords
PGE2; Th1/Th17; EP4 receptor; T cell differentiation
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
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