| First Author | Dai H | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 3 | Pages | 903-910 |
| PubMed ID | 28646040 | Mgi Jnum | J:250820 |
| Mgi Id | MGI:6100860 | Doi | 10.4049/jimmunol.1700418 |
| Citation | Dai H, et al. (2017) IL-23 Limits the Production of IL-2 and Promotes Autoimmunity in Lupus. J Immunol 199(3):903-910 |
| abstractText | The IL-23/IL-17 pathway is important in multiple autoimmune diseases, but its effect on lupus pathology remains unclear, with opposing trials in murine models of the disease. In this study, we show a disease activity-related upregulation of serum IL-23 and IL-23 receptor in patients with systemic lupus erythematosus (SLE) as compared with healthy controls. When added in SLE T cell in vitro cultures, IL-23 induced IL-17 and limited IL-2 production, whereas T follicular helper and double negative (DN) T cells significantly expanded. To further dissect the role of IL-23 in the expression of autoimmunity and related pathology, we generated IL-23 receptor-deficient MRL.lpr mice. These IL-23R(-/-)MRL.lpr mice displayed attenuated lupus nephritis with a striking decrease in the accumulation of DN T cells in the kidneys and secondary lymphoid organs. Moreover, T cells from IL-23R(-/-)MRL.lpr mice produced increased amounts of IL-2 and reduced amounts of IL-17 compared with T cells from wild type animals. In vitro IL-23 treatment promoted IL-17 production and downregulated IL-2 production. The IL-23R(-/-)MRL.lpr had fewer T follicular helper cells, B cells, and plasma cells, leading to decreased production of anti-dsDNA Abs. Our results show that IL-23 accounts for the main aspects of human and murine lupus including the expansion of DN T cells, decreased IL-2, and increased IL-17 production. We propose that blockade of IL-23 should have a therapeutic value in patients with SLE. |
