Journal article

Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p.

  • Zhou Y Johns Hopkins Asthma & Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md; Children's Hospital and the Institute of Biomedical Sciences and, Fudan University, and Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai, China.
  • Do DC Johns Hopkins Asthma & Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
  • Ishmael FT Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pa.
  • Squadrito ML Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Tang HM Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, Md.
  • Tang HL Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md.
  • Hsu MH Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pa.
  • Qiu L Johns Hopkins Asthma & Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md.
  • Li C Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Md.
  • Zhang Y Gene Expression & Genomics Unit, National Institute on Aging, National Institutes of Health, Baltimore, Md.
  • Becker KG Gene Expression & Genomics Unit, National Institute on Aging, National Institutes of Health, Baltimore, Md.
  • Wan M Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Md.
  • Huang SK Johns Hopkins Asthma & Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md; National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Lou-Hu Hospital, Shen-Zhen University, Shen-Zhen, China. Electronic address: skhuang@nhri.org.tw.
  • Gao P Johns Hopkins Asthma & Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: pgao1@jhmi.edu.
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  • 2017-06-21
Published in:
  • The Journal of allergy and clinical immunology. - 2018
English BACKGROUND
Mannose receptor (MRC1/CD206) has been suggested to mediate allergic sensitization and asthma to multiple glycoallergens, including cockroach allergens.


OBJECTIVE
We sought to determine the existence of a protective mechanism through which MRC1 limits allergic inflammation through its intronic miR-511-3p.


METHODS
We examined MRC1-mediated cockroach allergen uptake by lung macrophages and lung inflammation using C57BL/6 wild-type (WT) and Mrc1-/- mice. The role of miR-511-3p in macrophage polarization and cockroach allergen-induced lung inflammation in mice transfected with adeno-associated virus (AAV)-miR-511-3p (AAV-cytomegalovirus-miR-511-3p-enhanced green fluorescent protein) was analyzed. Gene profiling of macrophages with or without miR-511-3p overexpression was also performed.


RESULTS
Mrc1-/- lung macrophages showed a significant reduction in cockroach allergen uptake compared with WT mice, and Mrc1-/- mice had an exacerbated lung inflammation with increased levels of cockroach allergen-specific IgE and TH2/TH17 cytokines in a cockroach allergen-induced mouse model compared with WT mice. Macrophages from Mrc1-/- mice showed significantly reduced levels of miR-511-3 and an M1 phenotype, whereas overexpression of miR-511-3p rendered macrophages to exhibit a M2 phenotype. Furthermore, mice transfected with AAV-miR-511-3p showed a significant reduction in cockroach allergen-induced inflammation. Profiling of macrophages with or without miR-511-3p overexpression identified 729 differentially expressed genes, wherein expression of prostaglandin D2 synthase (Ptgds) and its product PGD2 were significantly downregulated by miR-511-3p. Ptgds showed a robust binding to miR-511-3p, which might contribute to the protective effect of miR-511-3p. Plasma levels of miR-511-3p were significantly lower in human asthmatic patients compared with nonasthmatic subjects.


CONCLUSION
These studies support a critical but previously unrecognized role of MRC1 and miR-511-3p in protection against allergen-induced lung inflammation.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/97099
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