Analysis of TGF-beta 1 and TGF-beta 3 as regulators of encephalitogenic Th17 cells: Implications for multiple sclerosis

作者：Lee Priscilla W; Yang Yuhong; Racke Michael K; Lovett Racke Amy E^*

来源：Brain, Behavior, and Immunity, 2015, 46: 44-49.

DOI：10.1016/j.bbi.2014.12.007

• Multiple sclerosis
• Experimental autoimmune encephalomyelitis
• TGF-beta 1
• TGF-beta 3
• T cell encephalitogenicity
• Th17 cells
• IL-23R
• GM-CSF

The phenotype of the CD4(+) T cells that mediate the CNS pathology in multiple sclerosis is still unclear, and yet a vital question for developing therapies. One of the conundrums is the role of TGF-beta in the development of encephalitogenic Th17 cells. In the present study, TGF-beta 1 and TGF-beta 3 were directly compared in their capacity to promote the differentiation of myelin-specific Th17 cells that could induce experimental autoimmune encephalomyelitis (EAE). Myelin-specific CD4(+) T cell receptor transgenic cells differentiated with antigen in the presence of IL-6+TGF-beta 1 or IL-6+TGF-beta 3 generated T cells that produced robust amounts of IL-17, but were incapable of inducing EAE when transferred into mice. Further analysis of these non-encephalitogenic Th17 cells found that they expressed lower amounts of GM-CSF or IL-23R, both molecules necessary for encephalitogenicity. Thus, TGF-beta, irrespective of isoform, negatively regulates the differentiation of encephalitogenic Th17 cells.

• 出版日期2015-5