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The role of LAIR-1 in the pathogenesis of autoimmune disease - Systemic sclerosis

Tuesday 7 April 2015

The role of LAIR-1 in the pathogenesis of autoimmune disease - Systemic sclerosis
Dr. Wioleta Marut/Prof. Timothy Radstake

Systemic sclerosis (SSc) is an autoimmune disorder, characterized by vascular abnormalities, immunological disturbances, and excessive over-production of collagen, resulting in skin thickening and fibrosis of internal organs. The mechanisms responsible for the initiation of SSc are largely unknown. Recent work from our group and others demonstrated that immune system deregulations are central in the pathogenesis of SSc. Inhibitory immune receptors play an important role in the regulation of the immune system. One of them, the leukocyte-associated immunoglobulin (Ig)-like receptor 1 (LAIR-1), expressed on the majority of immune cells, has collagens as abundantly available ligand. Collagen–LAIR-1 interactions inhibit cell activation and may, therefore, contribute to a dampening of the immune response. Since collagen is highly expressed in SSc tissues, we propose a role for this inhibitory receptor in the development of SSc. As a proof of concept we recently found that mice lacking LAIR-1 (LAIR-1 KO mice) have much stronger SSc phenotype when compare to wild type mice. However, further studies are needed to understand this process.

The main research questions are:
A) What is the role of LAIR-1 in the Bleomycin mice model of SSc?
B) Is LAIR-1 associated in progression and / or onset of inflammation and/or fibrosis?
C) What is the role of LAIR-1 in skin and lung fibrosis?

Cell biological and molecular techniques such as: Flow cytometry, Western blotting, IHC, IF, tissue embedding, luminex, cell culture, qPCR,
(mice handling will be performed by our technician).

6 - 9 months

Dr. W.Marut, Email: w.k.marut@umcutrecht.nl, tel +31 (0)88 755 3568