TSLP. A molecular modelling study
8 October 2018
UAntwerp, Campus Drie Eiken, Building Q, Auditorium O3 - Universiteitsplein 1 - 2610 Antwerp (Wilrijk) (route: UAntwerpen, Campus Drie Eiken
4:30 PM - 6:30 PM
Dries Van Rompaey
Hans De Winter - Pieter Van der Veken
Phd defence Dries Van Rompaey - Department of Pharmaceutical Sciences
The human body is under a constant state of attack by bacteria and other environmental pathogens. Our immune system encompasses a plethora of intricate and synergistic defence mechanisms, which can destroy these pathogens or render them harmless. However, this system is not perfect. In some patients, the immune system can mount a response to harmless particles, resulting in inflammation and associated symptoms.
This underlying predisposition has been termed atopy and can manifest in a number of ways. Three important chronic conditions have been linked to atopy: atopic rhinitis, asthma and atopic dermatitis. These three conditions are collectively known the atopic triad. In recent years, the pro-inflammatory cytokine Thymic Stromal Lymphopoietin (TSLP) has emerged as a key regulator in the development of atopic disease. It has likewise been implicated in chronic obstructive pulmonary disorder and cancer.
It engages in a complex with its cognate TSLP receptor and the interleukin-7 receptor alpha chain to elicit intracellular signalling, exerting far-reaching effects on the immune system. In this work, we investigate the dynamic behaviour of TSLP and probe several interesting structural features using a molecular dynamics approach. In silico techniques are used to identify the first small molecule inhibitors of TSLP signalling. Finally, the effects of TSLP in cancer are investigated by mining publicly available data for associations between patient survival and TSLP expression. Taken together,our findings contribute to an improved understanding of TSLP structure, dynamics and inhibition.