Kajsa Wing Group
The immune system is designed to protect the individual from pathogens while maintaining tolerance to self. Tolerance can be divided in central and peripheral tolerance. Central tolerance takes place in the thymus were T cells are selected and/or deleted in order to generate a non-auto reactive yet functional T cell repertoire. This system, however, is not perfect and all of us have self-reactive T cell in the circulation. To maintain peripheral tolerance Foxp3+ regulatory T cells (Tregs) have evolved and these cells that develop either in the thymus or in relation to peripheral immune responses, are absolutely critical for keeping the individual healthy. A better understanding of these concepts is critical for future development of treatment and prevention of arthritis and autoimmunity.
Foxp3+Tregs can suppress immune responses by inhibiting other T cells directly or indirectly via antigen presenting cells (APC). Since Tregs are unable to produce IL-2 they are dependant on what other cells produce. This creates a finely tuned balance between Treg, effector T cells (Teff) and APC that we have only begun to understand. Adapted from Wing et al. Trends Immunol 2011.
Foxp3+ Regulatory T cells
One objective in our group is to investigate the importance and function of Tregs in animal models of arthritis by using T cell receptor transgenic mice that recognize the prototypic self-antigen collagen type II. Previous experience has led us to believe that it is absolutely crucial to investigate Treg-mediated tolerance in an antigen-specific fashion. Another important part of the Treg-project is to investigate the specific role of different proteins expressed by Tregs, for autoimmunity in general and arthritis in particular. Some such as Cytotoxic T lymphocyte antigen-4 (CTLA-4) we have found to be important mediators of Treg suppression while others such as CD28 may have a role in homeostasis.
Spontaneous arthritis in SKG mice
Another objective is to develop a model of arthritis that occurs spontaneously as a complement to the collagen induced arthritis model. The basis for this project is the SKG mouse that develops arthritis in response to b-glucans or mannan from Saccharomyces cerevisiea. SKG mice have a mutation in the ZAP70 T cell receptor signaling protein that reduce the signal strength and leads to a more self-reactive T cell repertoire. By crossing the SKG mutation with other arthritis promoting genetic polymorphisms we are investigating the enhanced development of spontaneous arthritis. The model can be used both for testing of various disease pathways as well as to further investigate the antigen specificity and disease mechanism of SKG mice.
Kajsa Wing - Assistant Professor
Katrin Klocke - PhD student