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

67 Citations (Scopus)

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

Fingerprint

Systemic Lupus Erythematosus
Autoantibodies
B-Lymphocytes
RNA
Recombinases
Kidney Diseases
Helper-Inducer T-Lymphocytes
Autoimmunity
Transgenic Mice
Autoimmune Diseases
Disease Progression
Inflammation
T-Lymphocytes
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Hwang, S. H., Lee, H., Yamamoto, M., Jones, L. A., Dayalan, J., Hopkins, R., ... 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

B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice. / Hwang, Sun Hee; Lee, Huiyin; Yamamoto, Miwako; Jones, Leigh A.; Dayalan, Jivanaah; Hopkins, Richard; Zhou, Xin J.; Yarovinsky, Felix; Connolly, John E.; Curotto De Lafaille, Maria A.; Wakeland, Edward K.; Fairhurst, Anna Marie.

In: Journal of Immunology, Vol. 189, No. 12, 15.12.2012, p. 5786-5796.

Research output: Contribution to journalArticle

Hwang, SH, Lee, H, Yamamoto, M, Jones, LA, Dayalan, J, Hopkins, R, Zhou, XJ, Yarovinsky, F, Connolly, JE, Curotto De Lafaille, MA, Wakeland, EK & Fairhurst, AM 2012, 'B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice', Journal of Immunology, vol. 189, no. 12, pp. 5786-5796. https://doi.org/10.4049/jimmunol.1202195
Hwang, Sun Hee ; Lee, Huiyin ; Yamamoto, Miwako ; Jones, Leigh A. ; Dayalan, Jivanaah ; Hopkins, Richard ; Zhou, Xin J. ; Yarovinsky, Felix ; Connolly, John E. ; Curotto De Lafaille, Maria A. ; Wakeland, Edward K. ; Fairhurst, Anna Marie. / B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice. In: Journal of Immunology. 2012 ; Vol. 189, No. 12. pp. 5786-5796.
@article{799923474d6342b6a69f2d47f166e506,
title = "B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus - Prone mice",
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.",
author = "Hwang, {Sun Hee} and Huiyin Lee and Miwako Yamamoto and Jones, {Leigh A.} and Jivanaah Dayalan and Richard Hopkins and Zhou, {Xin J.} and Felix Yarovinsky and Connolly, {John E.} and {Curotto De Lafaille}, {Maria A.} and Wakeland, {Edward K.} and Fairhurst, {Anna Marie}",
year = "2012",
month = "12",
day = "15",
doi = "10.4049/jimmunol.1202195",
language = "English (US)",
volume = "189",
pages = "5786--5796",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84871122407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871122407&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1202195

DO - 10.4049/jimmunol.1202195

M3 - Article

VL - 189

SP - 5786

EP - 5796

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -