TICI-SLE | Understanding the Interaction of T cells and Immune Complexes in Systemic Lupus Erythematosus

Summary
Systemic Lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Immune complexes (ICs) are formed and deposited in various tissues, leading to inflammation and damage. T cells are part of the adaptive immune system, but also express innate-like receptors that could interact with ICs by binding complement factors or the constant region of immunoglobulins. However, the extent of these interactions and there relevance for the SLE pathogenesis has not been investigated so far. In the TICI-SLE project, we will analyze these interactions by 1) investigating the expression of receptors that could interact with ICs on T cells in the blood and inflamed tissue of SLE patients, 2) cultivating T cells with immune complexes and antibodies stimulating or blocking individual receptors, thereby elucidating the consequences of these interactions and 3) analyzing spatial T cell/IC interactions and their secondary consequences (like proinflammatory changes in stromal cells and chemoattraction of inflammatory cells) in skin samples from SLE patients. We hypothesize that T cell/IC interactions result in (co-)stimulation of T cells, leading to production of proinflammatory cytokines, cytotoxicity and induction of an inflammatory microenviornment. Understanding these interactions can then be exploited by the future development of therapeutics targeting these interactions. An additional focus of the project will be the personal development of the applicant and the dissemination and exploitation of project results.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101153683
Start date: 01-09-2024
End date: 31-08-2027
Total budget - Public funding: - 265 647,00 Euro
Cordis data

Original description

Systemic Lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Immune complexes (ICs) are formed and deposited in various tissues, leading to inflammation and damage. T cells are part of the adaptive immune system, but also express innate-like receptors that could interact with ICs by binding complement factors or the constant region of immunoglobulins. However, the extent of these interactions and there relevance for the SLE pathogenesis has not been investigated so far. In the TICI-SLE project, we will analyze these interactions by 1) investigating the expression of receptors that could interact with ICs on T cells in the blood and inflamed tissue of SLE patients, 2) cultivating T cells with immune complexes and antibodies stimulating or blocking individual receptors, thereby elucidating the consequences of these interactions and 3) analyzing spatial T cell/IC interactions and their secondary consequences (like proinflammatory changes in stromal cells and chemoattraction of inflammatory cells) in skin samples from SLE patients. We hypothesize that T cell/IC interactions result in (co-)stimulation of T cells, leading to production of proinflammatory cytokines, cytotoxicity and induction of an inflammatory microenviornment. Understanding these interactions can then be exploited by the future development of therapeutics targeting these interactions. An additional focus of the project will be the personal development of the applicant and the dissemination and exploitation of project results.

Status

SIGNED

Call topic

HORIZON-MSCA-2023-PF-01-01

Update Date

22-11-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.2 Marie Skłodowska-Curie Actions (MSCA)
HORIZON.1.2.0 Cross-cutting call topics
HORIZON-MSCA-2023-PF-01
HORIZON-MSCA-2023-PF-01-01 MSCA Postdoctoral Fellowships 2023