Type I interferon-dependent and -independent signaling underlie autoantibody production in a murine lupus model.

ABSTRACT: Systemic lupus erythematosus (SLE) is characterized by the development of autoantibodies against diverse self-antigens and damage to multiple organs. Immunization with the SLE autoantigen β2-glycoprotein I and lipopolysaccharide (LPS) induces a murine model of SLE with the sequential emergence of multiple hallmark SLE autoantibodies. LPS is a TLR4 trigger of innate immunity and inflammation that signals through adaptor proteins MyD88 and TRIF, resulting in the production of both inflammatory cytokines and type I interferons (IFN-I). We hypothesized that both IFN-I-dependent and -independent mechanisms are important in the initiation of SLE. Using our induced murine model of SLE, we found that TRIF deficiency completely abrogated autoantibody production. Downstream of TRIF, both IRF3 and IF

SUBMITTER: Levine JS 

PROVIDER: S-EPMC12908046 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature