TGF-? signaling initiated in dendritic cells instructs suppressive effects on Th17 differentiation at the site of neuroinflammation.

ABSTRACT: While the role of Transforming Growth Factor ? (TGF-?) as an intrinsic pathway has been well established in driving de novo differentiation of Th17 cells, no study has directly assessed the capacity of TGF-? signaling initiated within dendritic cells (DCs) to regulate Th17 differentiation. The central finding of this study is the demonstration that Th17 cell fate during autoimmune inflammation is shaped by TGF-? extrinsic pathway via DCs. First, we provide evidence that TGF-? limits at the site of inflammation the differentiation of highly mature DCs as a means of restricting Th17 cell differentiation and controlling autoimmunity. Second, we demonstrate that TGF-? controls DC differentiation in the inflammatory site but not in the priming site. Third, we show that TGF-? controls DC numbers at a precursor level but not at a mature stage. While it is undisputable that TGF-? intrinsic pathway drives Th17 differentiation, our data provide the first evidence that TGF-? can restrict Th17 differentiation via DC suppression but such a control occurs in the site of inflammation, not at the site of priming. Such a demarcation of the role of TGF-? in DC lineage is unprecedented and holds serious implications vis-à-vis future DC-based therapeutic targets.

SUBMITTER: Speck S 

PROVIDER: S-EPMC4114567 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature