| First Author | Keller EJ | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 2 | PubMed ID | 35055071 |
| Mgi Jnum | J:320964 | Mgi Id | MGI:6861221 |
| Doi | 10.3390/ijms23020874 | Citation | Keller EJ, et al. (2022) Spontaneous CD4+ T Cell Activation and Differentiation in Lupus-Prone B6.Nba2 Mice Is IFNAR-Independent. Int J Mol Sci 23(2) |
| abstractText | Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by dysregulated T and B lymphocytes. Type I interferons (IFN-I) have been shown to play important pathogenic roles in both SLE patients and mouse models of lupus. Recent studies have shown that B cell intrinsic responses to IFN-I are enough to drive B cell differentiation into autoantibody-secreting memory B cells and plasma cells, although lower levels of residual auto-reactive cells remain present. We speculated that IFN-I stimulation of T cells would similarly drive specific T-cell associated lupus phenotypes including the upregulation of T follicular helper cells and Th17, thereby affecting autoantibody production and the development of glomerulonephritis. Using the B6.Nba2 mouse model of lupus, we evaluated disease parameters in T cell specific IFN-I receptor (IFNAR)-deficient mice (cKO). Surprisingly, all measured CD4+ T cell abnormalities and associated intra-splenic cytokine levels (IFNgamma, IL-6, IL-10, IL-17, IL-21) were unchanged and thus independent of IFN-I. In contrast B6.Nba2 cKO mice displayed reduced levels of effector CD8+ T cells and increased levels of Foxp3+ CD8+ regulatory T cells, suggesting that IFN-I induced signaling specifically affecting CD8+ T cells. These data suggest a role for both pathogenic and immunosuppressive CD8+ T cells in Nba2-driven autoimmunity, providing a model to further evaluate the role of these cell subsets during lupus-like disease development in vivo. |
