Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus

A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-lambda) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a role for IFN-lambda in regulating both innate and adaptive immune responses, and increased serum concentrations have been described in multiple autoimmune diseases including SLE. Using the pristane-induced lupus model, we found that mice with defective IFN-lambda receptors (Ifnlr1(-/-)) showed increased survival rates, decreased lipogranuloma formation and reduced anti-dsDNA autoantibody titers in the early phase of autoimmunity development compared to pristane-treated wild-type mice. Moreover, Ifnlr1(-/-) mice treated with pristane had reduced numbers of inflammatory mononuclear phagocytes and cNK cells in their kidneys, resembling untreated control mice. Systemically, circulating B cells and monocytes (CD115(+)Ly6C(+)) were reduced in pristane-treated Ifnlr1(-/-) mice. The present study supports a significant role for type III interferons in the pathogenesis of pristane-induced murine autoimmunity as well as in systemic and renal inflammation. Although the absence of type III interferon receptors does not completely prevent the development of autoantibodies, type III interferon signaling accelerates the development of autoimmunity and promotes a pro-inflammatory environment in autoimmune-prone hosts.

Automated summary

The role of type III interferons in systemic lupus erythematosus has been increasingly studied, with evidence suggesting their involvement in regulating immune responses and promoting inflammation. In a lupus disease model, mice lacking type III interferon receptors showed improved survival rates, reduced autoantibody production, and decreased inflammatory cell infiltration in the kidneys, indicating a potential protective effect of inhibiting type III interferon signaling in autoimmunity development.