Allergies: the role of the TSLP protein
New study on allergies
Scientists at VIB-UGent have succeeded in unraveling the functioning of what is thought to be the 'master protein' that drives a range of common allergic diseases, such as asthma and eczema. At the molecular level, the team described how a protein called TSLP binds to its molecular partners on the surface of cells. This is the cornerstone of TSLP's bioactivity. These insights, published in the prestigious scientific journal Nature Communications, have also enabled the team to develop a new molecule capable of blocking TSLP activity. Given the molecule's promise in terms of developing new therapies for common allergies, the researchers are planning follow-up studies and seeking industrial partnerships.
Millions of people worldwide suffer from common allergies—ranging from mild asthma symptoms to severe atopic dermatitis, a common form of eczema. These diseases place a heavy burden on the quality of life of those who suffer from them, and at the same time have a huge socio-economic and health impact. The exact causes of these diseases are still unknown, although the answer probably lies in a combination of genetic, molecular, and environmental factors. Although some treatments can reduce the severity and frequency of symptoms, a complete cure has not yet been found.
To tackle the complex issue of studying diseases at the molecular level, Professor Savvas Savvides of the VIB-UGent Inflammation Research Center coordinated a multidisciplinary team led by Dr. Kenneth Verstraete, which brought together expertise from other VIB-UGent research centers: Ghent University, the University of Antwerp, the Pontifical Catholic University of Peru, and the University of Toulouse in France. The team focused on understanding the molecular and structural mechanism and how TSLP interacts with its two molecular receptors on the cell surface. A key aspect was explaining the three-dimensional structure of the TSLP-mediated molecular complex. In parallel, the team developed and characterized a new protein-based TSLP inhibitor that can effectively capture TSLP to prevent it from binding to its natural receptors on the cell surface. In this way, the bioactivity of TSLP can be blocked. The study was supported by funding from national and international sources, as well as European-level research infrastructure.
Prof. Savvas Savvides (VIB-UGent): “For the first time, we have obtained detailed snapshots of TSLP function. In particular, we have unraveled how TSLP mediates the protein complex on the cell surface responsible for several atopic diseases, including asthma and atopic dermatitis. TSLP has been the focus of many leading university laboratories around the world, as well as major pharmaceutical companies. This knowledge provides them with a new tool for therapeutic intervention. Our study demonstrates that basic research at the molecular level is the cornerstone for the development of new therapeutic strategies."
Prof. Rudi Beyaert (VIB-UGent): “The detailed structural and biochemical insights are a crucial source of information for understanding and optimizing the potency of our inhibitory molecule against TSLP. We are eager to see the implications and promise of this work.”
Future developments
Prof. Savvides' team is currently working closely with the partner team led by Rudi Beyaert and with the VIB's technology transfer department on follow-up studies, with a twofold objective: to optimize the TSLP inhibitor on the one hand, and to test the molecule in appropriate animal models for a range of allergies on the other.
Prof. Savvas Savvides (VIB-UGent): “We strongly believe in the potential of our discovery for the development of new therapies against allergies. At the same time, we hope that the insights and tools we have gained from this study will be catalysts for further developments in the field. The story of TSLP is far from over, as recent reports have added intriguing new twists to the function of TSLP. We will take advantage of our pole position in the field to continue contributing to our understanding of this fascinating protein. However, our priority now is to identify possible industrial partnerships to develop a real therapeutic tool."
Article:Structure and antagonism of the receptor complex mediated by human TSLP in allergy and asthma, Kenneth Verstraete, Frank Peelman, Harald Braun, Juan Lopez, Dries Van Rompaey, Ann Dansercoer, Isabel Vandenberghe, Kris Pauwels, Jan Tavernier, Bart N. Lambrecht, Hamida Hammad, Hans De Winter, Rudi Beyaert, Guy Lippens & Savvas N. Savvides, Nature Communications, doi: 10.1038/ncomms14937, published online April 3, 2017.
Translated by the author, source: medicalnewstoday.com
