4.3 Article

Ablation of SigH+ pDCs in B6.Nba2 mice prevents lupus-like disease development only if started before disease is fully established

Journal

LUPUS
Volume 31, Issue 13, Pages 1619-1629

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/09612033221127561

Keywords

lupus; plasmacytoid dendritic cell; B cell; Encephalomyocarditis virus

Categories

Funding

  1. Lupus Foundation of America (LIFELINE)
  2. National Institute of Allergy and Infectious Diseases [R01 AI118774, 5 R01 AI135922-36]

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This study reveals that ablation of pDCs needs to be initiated early and sustained in order to prevent the development of lupus-like disease. Furthermore, targeting pDCs does not affect general immunity.
Systemic lupus erythematosus is characterized by hyper-activation of the immune system, multi-organ inflammation, and end-organ damage. Type I interferons (IFN-I) have been strongly implicated a role in disease etiology as has the main IFN-I-producing cell subset, the plasmacytoid dendritic cell (pDC). The B6.Nba2 mouse model develops a lupus-like disease characterized by elevated IFN-I levels and pDC pathogenicity. We have previously shown that pDC ablation prior to disease development in B6.Nba2 mice effectively prevents disease; however, it remains unclear if a similar protection can be seen if pDC ablation is initiated during later disease stages. This is important as Systemic lupus erythematosus patients are rarely diagnosed until disease is well-established and thus preventative treatment is unlikely to take place. Here we show that ablation of pDCs in the B6.Nba2 mouse model must be initiated early in order to effectively block disease development and that sustained reduction in pDC numbers is necessary for sustained effects. Finally, targeting of pDCs have been hypothesized to affect immunity towards infectious agents, in particular virus and intracellular bacteria. We show here that pDC ablation in B6.Nba2 mice does not affect the anti-viral response to encephalomyocarditic virus or a model T-dependent antigen. In summary, pDC ablation does not affect general immunity, but needs to happen early and be sustained to prevent lupus-like disease development in B6.Nba2 mice.

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