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Dust-mite-derived protein disulfide isomerase suppresses airway allergy by inducing tolerogenic dendritic cells.
Liu, Xiaoyu; Wang, Yuwei; Chen, Desheng; Ji, Shuyu; Yang, Li-Teng; Huang, Qinmiao; Guan, Lvxin; Chang, Kexin; Li, Dan; Yuan, Ruyi; Ouyang, Chunyan; Hu, Tian-Yong; Liu, Zhi-Qiang; Sun, Baoqing; Xu, Guorong; Liu, Zhi-Gang; Yang, Ping-Chang.
Afiliación
  • Liu X; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Wang Y; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Chen D; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Ji S; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Yang LT; Department of Respirology, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
  • Huang Q; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Guan L; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Chang K; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Li D; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Yuan R; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Ouyang C; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.
  • Hu TY; Department of Allergy, Longgnag ENT Hospital, Shenzhen, China.
  • Liu ZQ; Department of Allergy, Longgnag ENT Hospital, Shenzhen, China.
  • Sun B; State Key Laboratory of Respiratory Disease, National Clinical Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. Electronic address: sunbaoqing@vip.163.com.
  • Xu G; School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
  • Liu ZG; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China. Electronic address: lzg@szu.edu.cn.
  • Yang PC; State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China. Electronic address: pc2356@163.com.
J Biol Chem ; 296: 100585, 2021.
Article en En | MEDLINE | ID: mdl-33771560
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Respiratorio / Células Dendríticas / Proteína Disulfuro Isomerasas / Pyroglyphidae / Hipersensibilidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Respiratorio / Células Dendríticas / Proteína Disulfuro Isomerasas / Pyroglyphidae / Hipersensibilidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Biol Chem Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos