TGF-beta as a promising option in the treatment of multiple sclerosis.
Transforming growth factor-beta (TGF-beta) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-beta in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. Among T cells, CD4+CD25+FOXP3+ T regs contain the main source of TGF-beta that suppresses immune responses in inflammatory sites. Defects in TGF-beta1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases. Thus, understanding the function and regulation of TGF-beta during immune responses offers therapeutic promise for the control of autoimmune diseases such as multiple sclerosis. However, the main mechanism by which TGF-beta exerts its protective effects on the experimental model of multiple sclerosis remains to be elucidated. Paradoxically, TGF-beta1 also acts as a pro-inflammatory cytokine and induces interleukin 17-producing pathogenic T helper cells (Th IL-17 cells) synergistically during an inflammatory response in which interleukin 6 is produced. In this review, we will describe the regulatory and therapeutic effects of TGF-beta in multiple sclerosis.
Mirshafiey
Abbas
A
Departmant of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran-14155, Box 6446, Iran. mirshafiey@tums.ac.ir
Mohsenzadegan
Monireh
M
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000276:immunology / Q000627:therapeutic use; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis / Q000276:immunology / Q000627:therapeutic use
D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2