Dendritic Cells Induce a Subpopulation of IL-12R square 2-Expressing Treg that Specifically Consumes IL-12 to Control Th1 Responses: e0146412

• Published in: PloS one Vol. 11; no. 1
• Main Authors: Sela, Uri, Park, Chae Gyu, Park, Andrew, Olds, Peter, Wang, Shu, Steinman[dagger], Ralph M, Fischetti, Vincent A
• Format: Journal Article
• Language: English
• Published: 01.01.2016
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0146412

Cytokines secreted from dendritic cells (DCs) play an important role in the regulation of T helper (Th) cell differentiation and activation into effector cells. Therefore, controlling cytokine secretion from DCs may potentially regulate Th differentiation/activation. DCs also induce de-novo generation of regulatory T cells (Treg) that modulate the immune response. In the current study we used the mixed leukocyte reaction (MLR) to investigate the effect of allospecific Treg on IL-12, TNF alpha and IL-6 secretion by DCs. Treg cells were found to markedly down-regulate IL-12 secretion from DCs following stimulation with TLR7/8 agonist. This down-regulation of IL-12 was neither due to a direct suppression of its production by the DCs nor a result of marked DC death. We found that IL-12 was rather actively consumed by Treg cells. IL-12 consumption was mediated by a subpopulation of IL-12R[Beta]2-expressing Treg cells and was dependent on MHC class-II expressed on dendritic cells. Furthermore, IL-12 consumption by Tregs increased their suppressive effect on T cell proliferation and Th1 activation. These results provide a new pathway of Th1 response regulation where IL-12 secreted by DCs is consumed by a sub-population of IL-12R[Beta]2-expressing Treg cells. Consumption of IL-12 by Tregs not only reduces the availability of IL-12 to Th effector cells but also enhances the Treg immunosuppressive effect. This DC-induced IL-12R[Beta]2-expressing Treg subpopulation may have a therapeutic advantage in suppressing Th1 mediated autoimmunity.