T cell-fibroblast interactive cell atlas in systemic sclerosis: Role of T cell exhaustion in tissue fibrosis

Concept

In recent years, accumulating evidence suggests that exhausted T cells (Tex) are of paramount importance for the maintenance of immunological self-tolerance and immune homeostasis. Tex are characterized by high expression of co-inhibitory receptors (CiR), and their key role is supported by the worsening of autoimmune diseases after depletion, or inhibition of, co-inhibitory molecules in mice, as well as in man. The purpose of this project was to examine T cell exhaustion and the role of Co inhibitory receptors( CiRs)  in the outcome of systemic sclerosis.

Facts and figures

Project lead
M Aspari
Aarhus University
au611635@uni.au.dk
FOREUM research grant: €50'000
2019–2020

Meet the team

M Aspari
Aarhus University
B Deleuran
Aarhus University
D Abraham
University College London
Stinne Greisen
Stinne Greisen Department of Biomedicine, Aarhus University
Voon H. Ong
UCL Medical School, Royal Free Campus
Christopher P. Denton
UCL Medical School, Royal Free Campus

Final Results

Projects implemented :

ELISA analysis of soluble CiRs. Analysis of extracellular expression of CiRs in by diseased T cells through flowcytometry. Different sub groups of PBMC’s including T and B cells were analysed for their expression of CiR’s and compared to healthy controls. Functional studies were carried out on SSc PBMC’s by blocking/stimulating PD1 and LAG 3 . The results from these experiments are promising.

Publications

EULAR Abstracts

2020

  • AB0151: Preliminary results show an increased expression of coinhibitory receptors in Systemic Sclerosis

Go to EULAR Abstract Archive

Lay Summary

The experimental nature of this research proposal limited the potential contribution of patient research partners. However, A project taskforce was setup at Aarhus University based on EULAR recommendations during the course of this project.


Coinhibitory receptors are molecules that regulate the functions of several immune cells and help to maintain a homeostatic balance. The functionality of these receptors can be utilized to regulate and or stabilize autoimmune responses in rheumatic diseases.