TY - JOUR
T1 - B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice
AU - Hwang, Sun Hee
AU - Lee, Huiyin
AU - Yamamoto, Miwako
AU - Jones, Leigh A.
AU - Dayalan, Jivanaah
AU - Hopkins, Richard
AU - Zhou, Xin J.
AU - Yarovinsky, Felix
AU - Connolly, John E.
AU - Curotto De Lafaille, Maria A.
AU - Wakeland, Edward K.
AU - Fairhurst, Anna Marie
PY - 2012/12/15
Y1 - 2012/12/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1202195
DO - 10.4049/jimmunol.1202195
M3 - Article
C2 - 23150717
AN - SCOPUS:84871122407
SN - 0022-1767
VL - 189
SP - 5786
EP - 5796
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -