title: TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology.
abstract: Studies have shown that transforming growth factor-beta (TGF-beta) and interleukin 6 (IL-6) are required for the lineage commitment of pathogenic IL-17-producing T helper cells (T(H)-17 cells). Unexpectedly, here we found that stimulation of myelin-reactive T cells with TGF-beta plus IL-6 completely abrogated their pathogenic function despite upregulation of IL-17 production. Cells stimulated with TGF-beta plus IL-6 were present in the spleen as well as the central nervous system, but they failed to upregulate the proinflammatory chemokines crucial for central nervous system inflammation. In addition, these cells produced IL-10, which has potent anti-inflammatory activities. In contrast, stimulation with IL-23 promoted expression of IL-17 and proinflammatory chemokines but not IL-10. Hence, TGF-beta and IL-6 'drive' initial lineage commitment but also 'restrain' the pathogenic potential of T(H)-17 cells. Our findings suggest that full acquisition of pathogenic function by effector T(H)-17 cells is mediated by IL-23 rather than by TGF-beta and IL-6.
authors.affiliation: Schering-Plough Biopharma, Palo Alto, California 94304, USA.
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: McGeachy
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Bak-Jensen
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Tato
authors.forename: Wendy
authors.initials: W
authors.lastname: Blumenschein
authors.forename: Terrill
authors.initials: T
authors.lastname: McClanahan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D013601:T-Lymphocytes / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D016753:Interleukin-10