Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by B cell hyperactivity leading to the production of various autoantibodies and subsequent development of glomerulonephritis, i.e. lupus nephritis. Among the principal targets of the autoantibodies produced in murine SLE are nucleic acid-protein complexes and the envelope glycoprotein gp70 of endogenous retroviruses. Recent studies have revealed that the innate receptor TLR7 plays a pivotal role in the development of a wide variety of autoimmune responses against DNA- and RNA-containing nuclear antigens, while TLR9 rather plays a protective role. In addition, the regulation of autoimmune responses against endogenous retroviral gp70 by TLR7 suggests the implication of endogenous retroviruses in this autoimmune response. Moreover, the demonstration that TLR7 is involved in the acute phase expression of serum gp70 uncovers an additional pathogenic role of TLR7 in murine lupus nephritis by promoting the expression of nephritogenic gp70 autoantigen. Clearly, the eventual identification of endogenous retroviruses implicated in murine SLE and of mouse genes regulating their production could provide a clue for the potential role of endogenous retroviruses in human SLE.