AI Article Synopsis
- TLRs help the immune system find and fight germs, but TLR8's job wasn't well understood before this study.
- Researchers looked at mice without TLR8 and found they had unusual immune responses, like overactive TLR7 and bigger spleens.
- Mice without TLR8 also showed symptoms of autoimmune disease, meaning their immune systems were attacking their own bodies.
Article Abstract
TLRs play an essential role in the induction of immune responses by detecting conserved molecular products of microorganisms. However, the function of TLR8 is largely unknown. In the current study, we investigated the role of TLR8 signaling in immunity in mice. We found that Tlr8(-/-) DCs overexpressed TLR7, were hyperresponsive to various TLR7 ligands, and showed stronger and faster NF-κB activation upon stimulation with the TLR7 ligand R848. Tlr8(-/-) mice showed splenomegaly, defective development of marginal zone (MZ) and B1 B cells, and increased serum levels of IgM and IgG2a. Furthermore, Tlr8(-/-) mice exhibited increased serum levels of autoantibodies against small nuclear ribonucleoproteins, ribonucleoprotein, and dsDNA and developed glomerulonephritis, whereas neither Tlr7(-/-) nor Tlr8(-/-)Tlr7(-/-) mice showed any of the phenotypes observed in Tlr8(-/-) mice. These data provide evidence for a pivotal role for mouse TLR8 in the regulation of mouse TLR7 expression and prevention of spontaneous autoimmunity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947223 | PMC |
| http://dx.doi.org/10.1172/JCI42081 | DOI Listing |
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