First Author | Yogev N | Year | 2012 |
Journal | Immunity | Volume | 37 |
Issue | 2 | Pages | 264-75 |
PubMed ID | 22902234 | Mgi Jnum | J:187367 |
Mgi Id | MGI:5436326 | Doi | 10.1016/j.immuni.2012.05.025 |
Citation | Yogev N, et al. (2012) Dendritic Cells Ameliorate Autoimmunity in the CNS by Controlling the Homeostasis of PD-1 Receptor(+) Regulatory T Cells. Immunity 37(2):264-75 |
abstractText | Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c(+) DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice. |