טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentTirosh Lior
SubjectCXCR6 and its Role in Autoimmune Processes
DepartmentDepartment of Biotechnology
Supervisor Professor Nathan Karin
Full Thesis text - in Hebrew Full thesis text - Hebrew Version


Abstract

CXCR6 is an inducible chemokine receptor that is expressed on subsets of T cells and its only known ligand is the transmembrane chemokine CXCL16. CXCR6 is found on effector and memory T-cells, but not on naïve ones. Interestingly, CXCR6 is not expressed on Th2 cells, but almost solely on Th1 and Tc1 - IFN-γ secreting cells. Th1 response is involved in several autoimmune diseases such as Rheumatoid Arthritis and Multiple Sclerosis (MS). In order to investigate the role of CXCR6 in the murine MS model - Experimental Autoimmune Encephalomyelitis (EAE) we have created a novel soluble receptor by fusing the extracellular N-terminal of CXCR6 with the FC region of IgG1 antibody heavy chain.

 In this study we have shown that administration of CXCR6IgG significantly decreases the clinical severity of ongoing EAE in mice. Cytokine secretion profile in MOG-restimulated spleen cells of CXCR6IgG-treated mice is characterized by a dramatic decrease in the secretion of IFN-γ, TNF-α, IL-2 and IL-12. This decrease demonstrates the decline in the type-1 inflammatory character of the splenocytes in the treated mice. In-vitro administration of CXCR6IgG to MOG restimulated splenocytes resulted a more moderate effect, but did cause a decrease in type-1 splenocyte percentage.

 We have shown that CXCR6 expressing cells, and the chemokine CXCL16, both play a role in the pathogenesis of EAE. We have created a novel soluble chemokine receptor that abated both EAE clinical signs and cell infiltration to the CNS. This soluble receptor, CXCR6IgG, has a therapeutic potential for Multiple Sclerosis treatment. The exact role of CXCR6 expressing cells and the mechanism of CXCR6IgG are not clear enough and they are further investigated in our laboratory.