B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice

Sun Hee Hwang, Huiyin Lee, Miwako Yamamoto, Leigh A. Jones, Jivanaah Dayalan, Richard Hopkins, Xin J. Zhou, Felix Yarovinsky, John E. Connolly, Maria A. Curotto De Lafaille, Edward K. Wakeland, Anna Marie Fairhurst

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of antinuclear autoantibodies. Antinuclear autoantibody development is recognized as one of the initial stages of disease that often results in systemic inflammation, kidney disease, and death. The etiology is complex, but it is clear that innate pathways may play an important role in disease progression. Recent data have highlighted an important role for the TLR family, particularly TLR7, in both human disease and murine models. In this study, we have presented a low copy conditional TLR7 transgenic (Tg7) mouse strain that does not develop spontaneous autoimmunity. When we combine Tg7 with the Sle1 lupus susceptibility locus, the mice develop severe disease. Using the CD19Cre recombinase system, we normalized expression of TLR7 solely within the B cells. Using this method we demonstrated that overexpression of TLR7 within the B cell compartment reduces the marginal zone B cell compartment and increases B and T cell activation but not T follicular helper cell development. Moreover, this enhanced B cell TLR7 expression permits the specific development of Abs to RNA/protein complexes and exacerbates SLE disease.

Original languageEnglish (US)
Pages (from-to)5786-5796
Number of pages11
JournalJournal of Immunology
Volume189
Issue number12
DOIs
StatePublished - Dec 15 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice'. Together they form a unique fingerprint.

  • Cite this

    Hwang, S. H., Lee, H., Yamamoto, M., Jones, L. A., Dayalan, J., Hopkins, R., Zhou, X. J., Yarovinsky, F., Connolly, J. E., Curotto De Lafaille, M. A., Wakeland, E. K., & Fairhurst, A. M. (2012). B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice. Journal of Immunology, 189(12), 5786-5796. https://doi.org/10.4049/jimmunol.1202195