Periodic Reporting for period 1 - DCBIO (In vivo functions of nuclear envelope rupture and antiviral specialization in dendritic cells)
Reporting period: 2018-02-01 to 2020-01-31
Viral infection of DCs impairs their immune functions. Unpublished data has revealed that in humans, the CD141+ DC subset is constitutively resistant to a broad range of enveloped viruses. Resistance was associated with the expression of the GTPase, RAB15. In the second objective of this project, the function of RAB15 in DC biology was investigated in vivo to study the division of antiviral labor among DC subsets.
Dissecting the mechanisms that regulate the immune system is critical for the development of novel therapeutic strategies including vaccines, anti-tumor therapies and other means of immunomodulation.
In the second objective, despite some initial technical difficulties in generating a colony of mutant mice with Rab15 deficiency we obtained encouraging preliminary data suggesting that Rab15 deficiency within dendritic cells accelerates disease progression following influenza A (PR1) infection. This finding will be further pursued once a larger colony is at our disposal.
Immunosenescence and aging of the immune system are important medical problems that are not well understood. An improved understanding of the mechanisms underpinning these processes is expected to reveal opportunities for therapeutic intervention. We believe our study may also reveal important markers of immunosenescence that could have clinical applications for monitoring aging within the immune system.