Forsøksdyr: Characterization of novel molecular pathways regulating migration of dendritic cells to lymph nodes (copy)

Godkjenningsdato 30.07.2018

Godkjenningsperiode 30.07.2018-31.12.2020

1) Purpose
Dendritic cells (DCs) are immune cells that patrol the body in order to find and take up antigens. After antigen uptake, DCs migrate quickly toward the draining lymph node, where they present antigens to T cells to initiate a specific immune response. We are particularly interested in studying the role of Rab proteins in the migration immune cells, specifically in DCs. Since we are extensively studying this subject in vitro but with some limitations due to the invitro systems, we'd like to further investigate whether and how Rab proteins influence migration in vivo. To achieve this, we will use a knockout mouse (KO) model in which the expression of our Rab of interest is conditionally depleted.

2) Expected distress for the animals
The procedure is expected to cause minimal-mild distress.

3) Expected scientific or societal benefit
The ability of DCs to migrate efficiently is central for the initiation of immune responses. However, the mechanisms involved in regulating DC migration are still not fully understood. A better understanding of how DC migration is regulated is important for the development of DC-based vaccines and treatment of immune disorders.

4) How demands for replacement, reduction and refinement will be adhered to
The described experiment will be part of a larger study and will supplement extensive in vitro experiments on cell cultures. However, to gain a better understanding of the physiological role of our Rab of interest, it is necessary to confirm our findings using an in vivo model. DC migration is highly affected by the complex microenvironments and signals found in the body, which cannot be completely mimicked in vitro.

The number of animals used will be kept to the minimum required for the analysis. This application describes pilot experiments that will be performed to determine the number of animals and refine our methods to minimize any pain or distress. As well the duration of the experiment will be kept as short as possible to minimize stress and discomfort. Due to possible painful inflammation and swelling at the injection site, the mice will receive analgesic treatment. Furthermore, animals will be provided soft bedding and single housing after the injection.