The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
TLR9 Regulates TLR7- and MyD88-Dependent Autoantibody Production and Disease in a Murine Model of Lupus
Open accessAbstract
Systemic lupus erythematosus is characterized by the production of autoantibodies against nucleic acid-associated Ags. We previously found that Tlr7 was required for anti-Sm and Tlr9 for anti-chromatin autoantibodies. Yet, although Tlr7 deficiency ameliorated disease, Tlr9 deficiency exacerbated it. Despite the mechanistic and clinical implications of this finding, it has yet to be elucidated. In this study, we characterize MRL/lpr lupus-prone mice genetically deficient in Tlr7, Tlr9, both Tlr7 and Tlr9, or Myd88 to test whether Tlr7 and Tlr9 function independently or instead regulate each other. We find that disease that is regulated by Tlr9 (and hence is worse in its absence) depends on Tlr7 for its manifestation. In addition, although Tlr7 and Tlr9 act in parallel pathways on different subsets of autoantibodies, Tlr9 also suppresses the production of Tlr7-dependent RNA-associated autoantibodies, suggesting previously unrecognized cross-regulation of autoantibody production as well. By comparing disease in mice deficient for Tlr7 and/or Tlr9 to those lacking Myd88, we also identify aspects of disease that have Tlr- and Myd88-independent components. These results suggest new models for how Tlr9 regulates and Tlr7 enhances disease and provide insight into aspects of autoimmune disease that are, and are not, influenced by TLR signals.
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Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
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Self-citationAIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
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Cited by
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577
Cancro, M. P. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-092419-031130 · Cited by 464
Gao, W., Xiong, Y., Li, Q., & Yang, H. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00508 · Cited by 353
Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex
Rizzetto, L., Fava, F., Tuohy, K. M., & Selmi, C. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.05.008 · Cited by 331
Altered B cell signalling in autoimmunity
Rawlings, D. J., Metzler, G., Wray-Dutra, M., & Jackson, S. W. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.24 · Cited by 308
Metadata
- Authors
- Nickerson, K. M., Christensen, S. R., Shupe, J., Kashgarian, M., Kim, D., Elkon, K., & Shlomchik, M. J.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-20
- Volume
- 184
- Issue
- 4
- Pages
- 1840-1848
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W20089701
- Cited by
- 347
- References
- 60
- FWCI
- 20.07
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: TLR9 Regulates TLR7- and MyD88-Dependent Autoantibody Production and Disease in a Murine Model of Lupus. https://app.cochat.ai/papers/10.4049/jimmunol.0902592
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- Nickerson, K. M., Christensen, S. R., Shupe, J., Kashgarian, M., Kim, D., Elkon, K., & Shlomchik, M. J. (2010). TLR9 Regulates TLR7- and MyD88-Dependent Autoantibody Production and Disease in a Murine Model of Lupus. The Journal of Immunology. https://doi.org/10.4049/jimmunol.0902592
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