Objective
Autoimmune skin diseases like psoriasis and atopic dermatitis are in part CD4 T cell mediated. After stimulation, CD4 T cells differentiate into different T helper cell lineages with distinct cytokine profiles. While in atopic dermatitis for example skin infiltrating T cells mainly show a Th2-polarization, in psoriasis, which is mediated by autoreactive T cells of the Th1-phenotype, recent evidence indicates an important pathogenic role for Th17 cells. However, it is not fully understood why a particular disease setting leads to a certain predominant T helper cell polarization and the consecutive skin phenotype. Given the high prevalence of psoriasis and atopic dermatitis in western countries, it is of great interest to elucidate the mechanisms of disease development and how they can be manipulated therapeutically.
Previously I have shown that Scurfy mice harbor autoreactive T cells recognizing antigens in the skin and developed the “Scurfy Transfer Model”. In this model autoreactive CD4 T cells from Scurfy mice are transferred into RAG-/- recipients and induce skin disease within 4 weeks. Thus I am now able to transfer either naive or different types of pre-differentiated CD4 T helper cells and to analyse the resulting skin phenotype. The following questions will be addressed: Which T helper cell polarization will spontaneously occur after transfer of naïve auto-reactive T cells into RAG-/- recipients? Which factors lead to that particular development? Which skin phenotype is induced after transfer of pre-differentiated Th1, Th2, Th9 and Th17 T helper cells? Are there shared phenotypic features of the induced skin phenotype and human autoimmune skin diseases? How can T helper cell polarization be manipulated in vivo?
In conclusion, the general objective of this research proposal is to evaluate the distinct skin pathologies induced by different T helper cell lineages derived from skin-autoreactive CD4 T cells in the “Scurfy Transfer Model”.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences cell biology cell polarity
- medical and health sciences basic medicine pathology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-RG
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
69120 HEIDELBERG
Germany
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