Speck, SuzanneLim, JamesShelake, SagarMatka, MarselStoddard, JonathanFarr, AlexanderKuchroo, VijayLaouar, Yasmina2014-09-082014Speck, Suzanne, James Lim, Sagar Shelake, Marsel Matka, Jonathan Stoddard, Alexander Farr, Vijay Kuchroo, and Yasmina Laouar. 2014. “TGF-β Signaling Initiated in Dendritic Cells Instructs Suppressive Effects on Th17 Differentiation at the Site of Neuroinflammation.” PLoS ONE 9 (7): e102390. doi:10.1371/journal.pone.0102390. http://dx.doi.org/10.1371/journal.pone.0102390.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:12785947While the role of Transforming Growth Factor β (TGF-β) 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-β 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-β extrinsic pathway via DCs. First, we provide evidence that TGF-β 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-β controls DC differentiation in the inflammatory site but not in the priming site. Third, we show that TGF-β controls DC numbers at a precursor level but not at a mature stage. While it is undisputable that TGF-β intrinsic pathway drives Th17 differentiation, our data provide the first evidence that TGF-β 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-β in DC lineage is unprecedented and holds serious implications vis-à-vis future DC-based therapeutic targets.en-USMedicine and Health SciencesImmunologyImmune CellsAntigen-Presenting CellsDendritic CellsAutoimmunityImmune SuppressionNeuroimmunologyJournal Article2014-09-0810.1371/journal.pone.0102390