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Counteracting immunopathology of rheumatic (autoimmune) diseases

Monday 4 May 2009

Dr. F.P.J.G. Lafeber

Project
Our department mainly focuses on inflammation and tissue damage in rheumatic diseases such as rheumatoid arthritis (RA), primary Sjogren syndrome (pSS) and osteoarthritis (OA). Using both clinical and experimental approaches, the final goal of our research is to develop novel therapeutic strategies. Questions that arise in clinical practice are studied in vitro and in animal in vivo models and are translated to clinical solutions (from bed to bench and back). In case of RA and pSS, in which primarily tissue inflammation causes tissue damage, we aim to counterbalance proinflammatory activity to prevent pathology. Within several lines of our research presently extra input and support is desired.

Reducing immunopathology in patients with pSS by selective effector T cell targeting
Patients with pSS suffer from chronic stimulation of the immune system. Several immunomodulatory therapies had very limited effects on inflammation and clinical symptoms, indicating a need for better therapies. There is evidence to suggest that IL-7Rα+ effector T cells play an important role in inflammation and tissue destruction in pSS. Selective targeting of this aggressive T cell population could be a novel treatment strategy for pSS. However, before such a therapy becomes a realistic approach the following questions need to be answered:

1. How do effector T cells and suppressive T cells influence proinflammatory and
tissue-destructive activity of B cells, macrophages and glandular tissue cells of
Sjögren patients?
2. Can specific targeting of effector T cells prevent inflammation and tissue
destruction?

IL-7-driven T cell/macrophage activation in RA
Chronic autoimmune joint inflammation causes severe pathology and movement impairment in RA patients. Recently, we have shown that a member of the IL-2 family, IL-7, is a potent proinflammatory cytokine that promotes experimental arthritis. Currently by using a microarray approach we are studying in detail the mechanisms IL-7 by which facillitates immunopathology. In this research line we want to address several questions:

1. How do candidate molecules mediate IL-7-induced T cell-dependent
monocyte/macrophage activation?
2. To what extent are these pathways resistant to anti-rheumatic therapies?

Techniques
Culture of human tissue and/or cells; MACS cell sorting to isolate T cells (and subsets) B cells and monocytes; cell phenotyping by FACS analysis; intra-cellular cytokine staining; cytokine assessment by ELISA; proliferation assays; immunohistochemistry.

Duration
6 or 9 months

Contact
General info: Floris Lafeber, 088 75 585 21, F.Lafeber@umcutrecht.nl
Detailed info: Joel van Roon, 088 75 597 58, J.vanRoon@umcutrecht.nl

More info
http://www.umcutrecht.nl/subsite/rheumatology-research

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