Abstract
Dendritic cells (DCs) are critical for instructing immune responses toward inflammatory or anti-inflammatory status. Heme oxygenase-1 (HO-1) is known for its cytoprotective effect against oxidative stress and inflammation, suggesting its immune regulatory role in allergic lung inflammation. HO-1 has been implicated in affecting DC maturation; however, its role in DC-mediated T-cell differentiation is unclear. In this study, we demonstrated that HO-1-expressing bone marrow-derived dendritic cells (BM-DCs) displayed tolerogenic phenotypes, including their resistance to lipopolysaccharide (LPS)-induced maturation, high level expression of IL-10, and low T-cell stimulatory activity. In addition, HO-1-expressing DCs were able to induce antigen-specific Foxp3+ regulatory T cells (Treg) differentiation in vitro and in vivo. Also, HO-1-expressing DCs modulated the severity of lung inflammatory responses in two murine models of airway inflammation. This study provided evidence supporting the role of HO-1-expressing DCs in tolerance induction and as a potential therapeutic target for allergic asthma as well as other inflammatory diseases.
Highlights
The lungs are the important organ in contact with external stimuli, including allergens, air pollutants, or infectious agents
Heme oxygenase-1 (HO-1) protein level was initially analyzed when bone marrow-derived dendritic cells (BM-Dendritic cell (DC)) were treated with Cobalt protoporphyrin-IX-chloride (CoPP) in various concentrations as CoPP is widely used as HO-1 inducer in vitro and in vivo
We observed that CoPP treatment significantly increased HO-1 protein expression in BM-DCs in a concentration-dependent manner regardless of LPS stimulation (S1 Fig)
Summary
The lungs are the important organ in contact with external stimuli, including allergens, air pollutants, or infectious agents. Heme oxygenases-1 (HO-1) activity in the lung represents an important defense mechanism. HO-1 degrades heme into free divalent iron, carbon monoxide and biliverdin, while these metabolites are known for the cytoprotective and anti-inflammatory effects in various disease contexts, including allogenic graft transplantation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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