TLR tolerance reduces IFN-alpha production despite plasmacytoid dendritic cell expansion and anti-nuclear antibodies in NZB bicongenic mice.

PloS One
Evelyn PauJoan E Wither

Abstract

Genetic loci on New Zealand Black (NZB) chromosomes 1 and 13 play a significant role in the development of lupus-like autoimmune disease. We have previously shown that C57BL/6 (B6) congenic mice with homozygous NZB chromosome 1 (B6.NZBc1) or 13 (B6.NZBc13) intervals develop anti-nuclear antibodies and mild glomerulonephritis (GN), together with increased T and B cell activation. Here, we produced B6.NZBc1c13 bicongenic mice with both intervals, and demonstrate several novel phenotypes including: marked plasmacytoid and myeloid dendritic cell expansion, and elevated IgA production. Despite these changes, only minor increases in anti-nuclear antibody production were seen, and the severity of GN was reduced as compared to B6.NZBc1 mice. Although bicongenic mice had increased levels of baff and tnf-α mRNA in their spleens, the levels of IFN-α-induced gene expression were reduced. Splenocytes from bicongenic mice also demonstrated reduced secretion of IFN-α following TLR stimulation in vitro. This reduction was not due to inhibition by TNF-α and IL-10, or regulation by other cellular populations. Because pDC in bicongenic mice are chronically exposed to nuclear antigen-containing immune complexes in vivo, we examined whether repeate...Continue Reading

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Citations

Jan 23, 2013·The Journal of Experimental Medicine·Francesca PreteFederica Benvenuti
Apr 2, 2016·Journal of Immunology Research·Xiaofeng LiaoXin M Luo
Aug 3, 2014·The Journal of Rheumatology·Amanda J SteimanDafna D Gladman
Oct 9, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaofeng LiaoXin M Luo

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Methods Mentioned

BETA
ELISA
flow cytometry
light microscopy
PCR

Software Mentioned

FlowJo

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