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Rab8a restores diverse innate functions of CD11b+CD11c+ dendritic cells from aged mice

ABSTRACT: Here, we demonstrate that Rab8a, a small GTPase, plays critical role in the functioning of dendritic cells (DCs) of aging host. Compared with the cells of young mice, CD11c+CD11b+ bone marrow derived dendritic cells (BMDCs) of aged mice generated a diminished type I IFN response when stimulated with Influenza A virus (IAV) and murine herpesvirus 68 (MHV68). In comparison to those of young mice, BMDCs of aged mice inefficiently presented exogenous antigens to CD8+ T cells in vitro and in vivo. While the Rab8a overexpressing BMDCs of aged animals regained functionality and generated a potent anti-viral IFN response, the Rab8a depleted cells of young animals were severely compromised in producing IFNs. BMDCs of young and aged animals were transcriptionally distinct but the Rab8a overexpressing cells of aged animals widely shared transcriptome with those of young animals. Ovalbumin fed Rab8a reconstituted BMDCs of aged animals upregulated Rab11 than did the control cells. Both Rab8a and Rab11 preferentially co-localised with the generated SIINFEKL peptide-H-2Kb complexes in the endosomal recycling compartment (ERC) to efficiently induce the surface display of such complexes. Compared with the control cells, the Ova fed Rab8a reconstituted BMDCs of aged animals expanded more of the TCR tg OT1 cells to better control IAV (WSN-SIINFEKL) infection. Therefore, targeting Rab8a might serve as a strategy to promote the functioning of DCs in the aging host to achieve favourable outcome of viral infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE279003 | GEO | 2024/10/14

REPOSITORIES: GEO

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