Régulation des gradients des chimiokines CXCL11 et CXCL10 par leur internalisation et dégradation via le récepteur CXCR3

 

Mélanie Girard

Centre de recherche du CHU Ste-Justine

 

Domaine : Maladies infectieuses et immunitaires

Programme : Formation de maîtrise

Concours 2016-2017

Partenaire:

Fondation des Étoiles

Chemokine receptors are cell-membrane proteins that induce cell migration in the body by following increasing chemokine gradients. The migration process is named chemotaxis and is essential to assure a variety of physiological processes during development and immune response. For example, chemotaxis allows immune cells to migrate towards an infection or inflammation site where it can participate in healing.

This project concerns CXCR3, a chemokine receptor found in large quantities on T cells and that induces migration of T cells towards sites of insult during immune reaction by chemotaxis following gradients of its chemokines CXCL9, CXCL10 and CXCL11. In many auto-immune diseases such as multiple sclerosis, inflammatory bowel syndrome and pathologic pregnancies, there is a novice over-stimulation of the immune system. CXCR3 over-activation could be implied in many of these diseases, possibly because it would increase immune cell recruitment without reason, which would damage tissues, which would increase immune response, creating never-ending inflammation.

The objectives are to understand better the mechanisms regulating chemokine gradients that attract CXCR3-expressing cells. An important mechanism that we study is chemokine internalization and degradation via cells that express specific chemokine receptors such as CXCR3. This mechanism allows elimination of chemokine from the extracellular compartment and gradient modulation and resorption.

This project will help to clarify pathologic and physiologic mechanisms regulating immune cell migration and could serve to the rational development of therapies for many auto-immune diseases.