Plasmacytoid dendritic cells from parent strains of the NZB/W F1 lupus mouse contribute different characteristics to autoimmune propensity

Yifan Zhan, Isabella Kong, Michael Chopin, Christophe Macri, Jian Guo Zhang, Jiaying Xie, Stephen L. Nutt, Meredith O'Keeffe, Edwin D. Hawkins, Eric F. Morand, Andrew M. Lew

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The NZB/W F1 (F1) mice develop severe disease that is similar to human systemic lupus erythematosus. By contrast, each parent strain, NZB or NZW, has limited autoimmunity, suggesting traits of both strains contribute to pathogenesis. Although many of the contributing genes have been identified, the contributing cellular abnormality associated with each parent strain remains unresolved. Given that plasmacytoid dendritic cells (pDCs) are key to the pathogenesis of lupus, we investigated the properties of pDCs from NZB and NZW mice. We found that NZB mouse had higher numbers of pDCs, with much of the increase being contributed by a more abundant CD8+ pDC subset. This was associated with prolonged survival and stronger proliferation of CD4+ T cells. By contrast, NZW pDCs had heightened capacity to produce interferon-α (IFNα) and IFNλ, and promoted stronger B-cell proliferation upon CpG stimulation. Thus, our data reveal the different functional and numerical characteristics of pDCs from NZW and NZB mouse.

Original languageEnglish
Pages (from-to)203-214
Number of pages12
JournalImmunology and Cell Biology
Volume98
Issue number3
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Apoptosis
  • interferon
  • lupus
  • plasmacytoid dendritic cells

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