The regulatory dendritic cell marker C1q is a potent inhibitor of allergic inflammation

Abstract

The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4 T cells with a suppressive activity. Furthermore, C1q expression is upregulated in peripheral blood mononuclear cells of allergic patients in the course of successful allergen immunotherapy. Herein, we investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin (OVA) or birch pollen (BP)-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness (AHR), eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs. Administration of C1q does not expand IL-10/Foxp3 regulatory T cells in the lungs, spleen, or in the blood. Depletion of plasmacytoid dendritic cells (pDCs) abrogates the capacity of C1q to reduce AHR and eosinophilic infiltrates in OVA-sensitized mice. Also C1q treatment inhibits the activation of human and mouse pDCs by CpGs, thereby demonstrating a critical role for pDCs in the anti-inflammatory activity of C1q. We conclude that regulatory dendritic cells can mediate a potent direct anti-inflammatory activity via the expression and/or secretion of molecules such as C1q, independently of their capacity to expand the pool of regulatory T cells.

Cigarette smoke–induced reduction of C1q promotes emphysema

“…Whereas the onset of autoimmunity in C1q -/mice is highly age dependent, we found early evidence for aberrant T cell activation, albeit milder, in 5-month-old mice. Short-term intraperitoneal injection of C1q in a model of allergic airway diseases failed to show a significant expansion of Treg cells in blood, the lungs, and the spleen (46). These findings are in contrast with chronic and lung-specific (e.g., intratracheal) administration of C1q results in potent upregulation of Tregs and decreased inflammation in the airways, suggesting localized induction of Tregs that control inflammation.…”

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

“…There are also other molecules that can be regarded as the biomarkers of Tol-DC. The complement subunit C1q was recently identified as a biomarker for monocyte-derived Tol-DC, which could suppress CD4 + T-cell activation via increasing IL-10 secretion ( 24 ). Immature DC are a rich source of active C1q, and the expression of C1q is downregulated when DC are approaching the mature state ( 25 ).…”

Advances and highlights in allergen immunotherapy: On the way to sustained clinical and immunologic tolerance

“…Expression or secretion of molecules, such as C1q, can confer a potent direct anti-inflammatory function to regulatory DCs independent of their capacity for expanding the pool of Treg cells. 120 AIT combined with biological agents and probiotics Studies on the combination of biological agents with AIT seemed more and more frequent in recent years. A combined therapy comprising a probiotic together with peanut OIT was recently reported.…”