Abstract
TGF‐β promotes either effector or regulatory T cell differentiation depending upon other cytokines in the local environment. While IL‐2 and TGF‐β induce naive T cells to become Foxp3+ regulatory cells (iTregs), the combination of IL‐6 and TGF‐β induce pro‐inflammatory IL‐17‐producing cells (Th17). Others have reported that IL‐6 can utilize TGF‐β produced by thymus‐derived natural Treg cells (nTreg) to convert them to Th17. We report that TGF‐β‐induced Tregs were completely resistant to IL‐6, and Foxp3 expression and suppressive activity in vitro and in vivo was unaffected. We then observed that the combination of IL‐2 and TGF‐β enables nTregs to also become resistant to IL‐6 by down‐regulating IL‐6R. Thus, besides generating iTregs, IL‐2 and TGF‐β stabilizes the suppressive phenotype of nTregs. The different sensitivities of Foxp3+ nTregs and iTregs to IL‐6 may reflect different roles for these two subsets in the adaptive immune response, and emphasizes the central role of the combination of IL‐2 and TGF‐β to control immunologic homeostasis.This work was supported by grants from the Arthritis National Research Foundation, Clinical Research Feasibility Fund, James H. Zumberge Faculty Research Innovation Fund, the Arthritis Foundation, ExCell Therapeutics, Nora Eccles Treadwell Foundation, and BD Biosciences.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
