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Functional characterization of the novel human cytokine TSLP and its role in health and disease


Cytokines form a family of specialized proteins that mediate communication between immune cell-types. They play a central role in the initiation and regulation of the immune response. Thymic stromal lymphopoietin (TSLP) is a recently discovered cytokine and thus constitutes an emerging area of research in immunology. We were the first to describe the function of this novel cytokine. Human TSLP is produced by epithelial, stromal and mast cells. It functions by activating myeloid CD11c+ dendritic cells, which subsequently modulate the T cell immune response. Although there is a strong functional and pathological link between human TSLP and allergy, preliminary data show that TSLP is produced in other types of inflammation. Besides our early work, the biology and disease association of human TSLP remain largely unknown.

The objective of this proposal is to study the role of human TSLP in the immune system and in the pathophysiology of immune-related diseases using three different approaches:
1) Study of TSLP-activated CD11c+ dendritic cells and their interaction with T cells, B cells and NK cells;
2) molecular characterization of TSLP function using large-scale transcriptional analysis of TSLP-activated cells, and study of selected TSLP-induced genes in terms of expression profile, regulation and function;
3) Assessment of the in situ production of TSLP by immuno-histology in a broad array of diseases.

Our research project should help identify new cellular and molecular pathways regulating immune responses. The in situ study of TSLP could shed new light in the pathophysiology of immune-related diseases such as allergy, infectious diseases and cancer. TSLP and/or TSLP-induced molecules could serve as diagnostic/prognostic markers or constitute new therapeutic targets. The constitution of a European pole of excellence in the study of human TSLP will increase the attractiveness and competitiveness of European research in immunology and related fields.

Call for proposal

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