Advisory Committee Chair
Chander Raman
Advisory Committee Members
Robert Sorge
Christianne Strang
Edwin Cook
Andrzej Slominski
Nabiha Yusuf
Document Type
Dissertation
Date of Award
2021
Degree Name by School
Doctor of Philosophy (PhD) College of Arts and Sciences
Abstract
TGFβR3 is a membrane bound co-receptor to many members of the TGFβ superfamily of ligands and is broadly expressed in the human body. TGFβR3 is known to modulate immune system function, but its exact role is at this time poorly understood. Work by Aleman-Muench et al., (2012) suggests that TGFβR3 regulates T cell development in the thymus. In order to further investigate the role of TGFβR3 in the immune system our lab developed a mouse which lacks TGFβR3 selectively in mature T cells. The contribution of TGFβR3 on in vivo activation and differentiation of T cells was investigated by utilizing experimental autoimmune encephalomyelitis (EAE), the mouse model to study multiple sclerosis (MS). The effect of TGFβR3 on the proliferation and differentiation of CD4+ T cells was also investigated with in vitro methods. We found that mice lacking TGFβR3 in mature T cells develop more severe EAE induced by active immunization with myelin oligodendrocyte (MOG) peptide or by passive transfer of encephalitogenic Th17 T cells, but not encephalitogenic Th1 cells. Increased severity of EAE in MOG immunized TGFβR3 null mice was associated with expansion of IFNγ expressing CD4 T cells in the spinal cord. In vitro TGFβR3 loss of function had no effect on T cell proliferation or differentiation into Th1 or Th17 cells. These results suggest that TGFβR3 plays a role in limiting CD4+ T cell polarization towards pathogenic effector cell populations. Also, data emerging from our lab suggests that TGFβR3 may function to limit the transdifferentiation of pathogenic Th17 cells towards a Th1 phenotype. These data suggest that TGFβR3 acts to restrict EAE disease severity by inhibiting the transdifferentiation of IL-17 producing Th17 towards more pathogenic IFNγ producing Th1 cells.
Recommended Citation
Duesman, Samuel, "The Function Of Tgfβr3 (Betaglycan) In The Differentiation And Proliferation Of T Cells" (2021). All ETDs from UAB. 778.
https://digitalcommons.library.uab.edu/etd-collection/778