Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis?
Our understanding of the pathophysiology of multiple sclerosis (MS) has evolved significantly over the past two decades as the fields of immunology and neurobiology provide new avenues of exploration into the cause and mechanism of the disease. It has been known for decades that T cells have different cytokine phenotypes, yet the cytokine phenotype of pathogenic T cells in MS is still an area of debate. In EAE, it appears that IFNγ and IL-17, produced by Th1 and Th17 cells respectively, are not the critical factor that determines T cell encephalitogenicity. However, there are molecules such as IL-23, T-bet and STAT4, that appear to be critical, yet it is unclear whether all these molecules contribute to a common, yet undefined pathway, or act in a synergistic manner which culminates in encephalitogenicity has still to be determined. Therefore, the focus of research on effector T cells in MS should focus on pathways upstream of the cytokines that define Th1 and Th17 cells, since downstream products, such as IFNγ and IL-17, probably are not critical determinants of whether an effector T cells is capable of trafficking to the CNS and inducing inflammatory demyelination.
Lovett-Racke
Amy E
AE
Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Medical Center, Columbus, OH 43210, USA. Amy.Lovett-Racke@osumc.edu
Yang
Yuhong
Y
Racke
Michael K
MK
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology*; D050797:STAT4 Transcription Factor / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D050797:STAT4 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma