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Updated: Nov 11, 2025
Analysis of Pulmonary Dendritic Cell Maturation and Migration during Allergic Airway Inflammation
Published on: July 23, 2012
Dust-mite-derived protein disulfide isomerase suppresses airway allergy by inducing tolerogenic dendritic cells
Xiaoyu Liu1, Yuwei Wang1, Desheng Chen1
1State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
Abstract:
House dust mites (HDMs) are a potent allergen source that are commonly found in human living environments. While HDMs are known to induce allergic diseases in humans, such as asthma, its other biological activities related to human health are less understood. Our laboratory recently purified the HDM protein PDI (protein disulfide isomerase). In this study, we assess the role of PDI in contributing to immune regulation. Using mass spectrometry, we analyzed the complexes of DEC205 and HDM extracts, and the role of PDI in the induction of tolerogenic dendritic cells (DCs) was assessed in human cell culture experiments and verified in a murine model. We found that more than 20 HDM-derived proteins, including PDI, bound to DCs by forming complexes with DEC205. Additionally, DEC205-mediated the endocytosis of PDI. HDM-derived PDI (HDM-PDI) promoted Foxp3 expression in DCs. HDM-PDI-primed DCs also showed tolerogenic properties that induced regulatory T cell development, indicating that the primed DCs were tolerogenic DCs. Our results suggested that the PDI/DEC205/TIEG1/Foxp3 signal pathway activation was involved in the HDM-PDI-induced Foxp3 expression in DCs. Finally, we found that HDM-PDI competitively counteracted the Th2 cytokines to restore DC's tolerogenicity, and administration of HDM-PDI could suppress experimental asthma. In conclusion, our data suggest that HDM-PDI contributes to immune regulation by inducing tolerogenic DC development. Administration of HDM-PDI can alleviate experimental asthma. These findings demonstrate that HDM-PDI has translational potential to be used in the treatment of immune disorders such as asthma.
Insights
House dust mite protein PDI induces immune tolerance by promoting regulatory T cells. This protein can alleviate experimental asthma, showing potential for treating immune disorders.
Area of Science:
- Immunology
- Allergology
- Protein biochemistry
Background:
- House dust mites (HDMs) are common allergens linked to asthma.
- The immune regulatory functions of HDM-derived proteins are not fully understood.
- Protein disulfide isomerase (PDI) from HDMs was recently purified.
Purpose of the Study:
- To investigate the role of HDM-derived PDI in immune regulation.
- To assess PDI's ability to induce tolerogenic dendritic cells (DCs).
- To evaluate PDI's therapeutic potential for allergic diseases like asthma.
Main Methods:
- Mass spectrometry to identify HDM protein complexes with DEC205 on DCs.
- In vitro human cell culture to assess PDI's effect on DCs and T cells.
- In vivo murine model to verify findings and test PDI's efficacy in experimental asthma.
Main Results:
- Over 20 HDM proteins, including PDI, bind to DCs via DEC205-mediated endocytosis.
- HDM-PDI promotes Foxp3 expression in DCs, leading to tolerogenic DC development.
- HDM-PDI counteracts Th2 cytokines, restores DC tolerogenicity, and suppresses experimental asthma.
Conclusions:
- HDM-PDI induces immune tolerance by promoting tolerogenic DCs and regulatory T cells.
- HDM-PDI administration can alleviate experimental asthma.
- HDM-PDI shows translational potential for treating immune disorders such as asthma.
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