| First Author | Luu T | Year | 2021 |
| Journal | PLoS One | Volume | 16 |
| Issue | 4 | Pages | e0250340 |
| PubMed ID | 33891644 | Mgi Jnum | J:307318 |
| Mgi Id | MGI:6710115 | Doi | 10.1371/journal.pone.0250340 |
| Citation | Luu T, et al. (2021) Priming of myelin-specific T cells in the absence of dendritic cells results in accelerated development of Experimental Autoimmune Encephalomyelitis. PLoS One 16(4):e0250340 |
| abstractText | Experimental autoimmune encephalomyelitis (EAE) is an established animal model of multiple sclerosis (MS). Inflammatory CD4+ T cell responses directed against CNS antigens, including myelin proteolipid protein (PLP), are key mediators of EAE. Dendritic cells (DCs) are critical for the induction of T cell responses against infectious agents. However, the importance of DCs in priming self-reactive CD4+ T cells in autoimmune disease such as MS has been unclear. To determine the requirement of DCs in PLP-specific CD4+ T cell responses and EAE, we genetically deleted CD11c+ DCs in PLP T cell receptor (TCR) transgenic SJL mice constitutively. DC deficiency did not impair the development, selection or the pathogenic function of PLP-specific CD4+ T cells in these mice, and resulted in accelerated spontaneous EAE compared to DC sufficient controls. In addition, using a genetic approach to ablate DCs conditionally in SJL mice, we show that CD11c+ DCs were dispensable for presenting exogenous or endogenous myelin antigen to PLP-specific T cells and for promoting pro-inflammatory T cell responses and severe EAE. Our findings demonstrate that constitutive or conditional ablation of CD11c+ DCs diminished self-tolerance to PLP autoantigen. They further show that in the absence of DCs, non-DCs can efficiently present CNS myelin antigens such as PLP to self-reactive T cells, resulting in accelerated onset of spontaneous or induced EAE. |
