„Regulation of cutaneous tissue-repair by a specialized population of CD4+ T cells“
Consortium: Daniel J. Campbell (Benaroya Research Institute at Virginia Mason) und Iris Gratz (PLUS). Sum (part Iris Gratz): $726,650 (approx. 610,000€). R01 National Institute of Health (NIH) grant R01AI127726 (Role: PI).
In healthy individuals T cells in the skin not only combat infection but also work in concert to help maintainnormal tissue homeostasis and promote sterile tissue repair. We have identified a novel population of CLA+CD4+ T cells in the peripheral blood and skin of healthy subjects, and we hypothesize that this is a regulatory population of skin-tropic T cells that participates in the host-protective antimicrobial andwound healing responses following tissue damage. In this proposal, we will use in vitro analyses and innovative humanized mouse models to test this hypothesis, assessing the developmental origins of CLA+CD103+ cells and their relationship to other populations of skin T cells, and assessing their function during cutaneous inflammation and wound healing.
STUDIES ON THE BIOLOGY OF IgE AND SPECIFICALLY ON THE REGULATION OF IgE RESPONSE IN VIVO
Project leader: Mag. Dr. Gertrude Achatz
Period 01.01.2013 – 31.12.2015
In the last years, many working groups, including ourselves, have described several B cell specific control mechanisms that indicate a tight control of the IgE response, impressively reflected in a 1000 – 10,000 fold difference in the steady state serum levels of IgE compared to IgG1 in mice. Nevertheless, the precise understanding of the IgE regulation and its biological function is, at best, limited. With the current project proposal we want to gain deeper insights into both, by focusing on two independent but related topics: 1) Chemokine expression of Th1 and Th2 dependent Ig-isotypes; 2) Construction of an IgE/IgA only mouse. 1) In general, chemokines and their receptors play an important role in the regulation of the development and maintenance of immune responses. In the first part of the present project proposal, we want to analyze and compare the distinct signal transduction of Th1 and Th2 dependent Ig-isotypes. Genomic and proteomic approaches will be performed to evaluate isotype-specific chemokine expression patterns. 2) In a different but synergistic approach, the humoral immune response of IgE will be further analyzed by constructing a mouse strain exclusively expressing IgE/IgA. This mouse strain will be a perfect tool to study the biological relevance of the IgE response during humoral immunity and to describe the development and maintenance of IgE memory. In our opinion, these two promising strategies together are an ideal and unique way to study the in vivo function of the IgE immunoglobulin itself, the IgE antigen receptor and therewith connected isotype-specific signal transduction. We are convinced our findings will provide new insights into the biology of IgE development and the maintenance of the IgE response in vivo.
IMMUNITY IN CANCER AND ALLERGY
(FWF Project DK-Plus W1213)
The mammalian immune system acts as a complex surveillance system ensuring to distinguish between self and non-self, and between harmless and dangerous events approaching from outside or inside of the organism. Moreover, it interacts with growth, differentiation and death of cells and tissues, and thus maintains the homeostasis and the integrity of our body. The doctoral college is focused on two pathologies of the immune system, i.e. the overwhelming allergic immune response and the inefficient immune response against certain tumors. Both diseases are a growing concern and there is an urgent medical need to elucidate the underlying mechanisms for the development of new therapies. Unraveling the cellular and molecular immunological mechanisms and pathways enables to develop rational and molecule-based strategies for the treatment of these diseases. The aim of the doctoral college is to attract and select excellent graduate students from all over the world, to provide an intellectually stimulating environment, an excellent instrumental and methodological infrastructure and ambitious scientific projects, and to prepare for a successful career in basic as well as translational and applied science. The college comprises ten research groups. Their track records, experience with national and international programs, and their excellent infrastructure guarantees high quality research and training. Furthermore, the college structure ensures that students benefit from the collective experience of the researchers.