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Bruce Butler. And Zhu A Hoffman, who won a quarter of the 2011 Nobel Prize in Physiology or Medicine. Bruce A. Beutler and Jules A. Hoffmann are professors and chairmen of the Department of Genetics because of their discovery in activating innate immunity and Ralph M. Steinman Beutler is a professor and chairman of the Department of Genetics, Ernest Beutler of Scripps Research Institute in La Jolla, California, his father, a hematologist and medical geneticist, is also a professor and dean of Scripps.
布鲁斯·巴特勒。与朱A.霍夫曼,他获得2011年诺贝尔生理学或医学奖四分之一。布鲁斯·巴特勒(Bruce A. Beutler)和朱尔斯·霍夫曼(Jules A. Hoffmann)因为在激活先天免疫方面的发现以及拉尔夫·斯坦曼(Ralph M.Steinman)Beutler是遗传学系教授及主席,美国加利福尼亚州拉霍亚的斯克里普斯研究所,欧内斯特Beutler,他的父亲,一个血液学家和医学遗传学家,也是Scripps教授和系主任。
https://pubmed.ncbi.nlm.nih.gov/23589617/
http://www.pubmedplus.cn/P/SearchQuickResult?wd=d1c31aa9-e550-409d-8efc-79b7eebc4b00
J Immunol
. 2013 May 15;190(10):4982-90.
doi: 10.4049/jimmunol.1202986. Epub 2013 Apr 15.
Affiliations expand
PMID: 23589617
PMCID: PMC3729324
Free PMC article
Nucleic acid (NA)-sensing TLRs (NA-TLRs) promote the induction of anti-nuclear Abs in systemic lupus erythematosus. However, the extent to which other nonnuclear pathogenic autoantibody specificities that occur in lupus and independently in other autoimmune diseases depend on NA-TLRs, and which immune cells require NA-TLRs in systemic autoimmunity, remains to be determined. Using Unc93b1(3d) lupus-prone mice that lack NA-TLR signaling, we found that all pathogenic nonnuclear autoantibody specificities examined, even anti-RBC, required NA-TLRs. Furthermore, we document that NA-TLRs in B cells were required for the development of antichromatin and rheumatoid factor. These findings support a unifying NA-TLR-mediated mechanism of autoantibody production that has both pathophysiological and therapeutic implications for systemic lupus erythematosus and several other humoral-mediated autoimmune diseases. In particular, our findings suggest that targeting of NA-TLR signaling in B cells alone would be sufficient to specifically block production of a broad diversity of autoantibodies.
Disclosures
The authors have no financial conflicts of interest.
FIGURE 1
NA-TLRs are required for development…
FIGURE 2
Lupus-associated dermatitis in MRL- Fas…
FIGURE 3
Total isotype and subclass Ig…
FIGURE 4
ANA specificities and IgM RF…
FIGURE 5
Nonnuclear autoantibody levels in 3d…
FIGURE 6
The effect of NA-TLR deficiency…
All figures (7)
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Animals
Antibodies, Antinuclear / immunology*
Antibody-Producing Cells / immunology
Autoantibodies / immunology
B-Lymphocytes / immunology*
Bone Marrow Cells / cytology
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology
Chromatin / immunology
Dendritic Cells
Female
Immunologic Deficiency Syndromes
Lupus Erythematosus, Systemic / immunology
Lymphocyte Activation / immunology
Macrophages / immunology
Membrane Glycoproteins / immunology*
Membrane Transport Proteins / immunology
Mice
Mice, Inbred NZB
Myeloid Differentiation Factor 88 / immunology
Nucleic Acids / immunology*
Primary Immunodeficiency Diseases
Rheumatoid Factor / immunology
Ribonucleoproteins / immunology
Signal Transduction
Toll-Like Receptor 7 / immunology*
Toll-Like Receptor 9 / immunology*
Antibodies, Antinuclear
Autoantibodies
Chromatin
Membrane Glycoproteins
Membrane Transport Proteins
Myd88 protein, mouse
Myeloid Differentiation Factor 88
Nucleic Acids
Ribonucleoproteins
Tlr7 protein, mouse
Tlr9 protein, mouse
Toll-Like Receptor 7
Toll-Like Receptor 9
UNC93B1 protein, mouse
Rheumatoid Factor
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