Plasmacytoid Dendritic Cells and C1q Differentially Regulate Inflammatory Gene Induction by Lupus Immune Complexes
- 15 January 2012
- journal article
- research article
- Published by The American Association of Immunologists
- Vol. 188 (2), 902-915
- https://doi.org/10.4049/jimmunol.1102797
Abstract
Immune complexes (ICs) play a pivotal role in causing inflammation in systemic lupus erythematosus (SLE). Yet, it remains unclear what the dominant blood cell type(s) and inflammation-related gene programs stimulated by lupus ICs are. To address these questions, we exposed normal human PBMCs or CD14+ isolated monocytes to SLE ICs in the presence or absence of C1q and performed microarray analysis and other tests for cell activation. By microarray analysis, we identified genes and pathways regulated by SLE ICs that are both type I IFN dependent and independent. We also found that C1q-containing ICs markedly reduced expression of the majority of IFN-response genes and also influenced the expression of multiple other genes induced by SLE ICs. Surprisingly, IC activation of isolated CD14+ monocytes did not upregulate CD40 and CD86 and only modestly stimulated inflammatory gene expression. However, when monocyte subsets were purified and analyzed separately, the low-abundance CD14dim (“patrolling”) subpopulation was more responsive to ICs. These observations demonstrate the importance of plasmacytoid dendritic cells, CD14dim monocytes, and C1q as key regulators of inflammatory properties of ICs and identify many pathways through which they act.Keywords
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