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

Yufeng Zhou, Danh C. Do, Faoud T. Ishmael, Mario Leonardo Squadrito, Ho Man Tang, Ho Lam Tang, Man Hsun Hsu, Lipeng Qiu, Changjun Li, Yongqing Zhang, Kevin G. Becker, Mei Wan, Shau Ku Huang, Peisong Gao

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)350-364.e8
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number1
DOIs
Publication statusPublished - Jan 1 2018
Externally publishedYes

Fingerprint

Cockroaches
Macrophages
Inflammation
prostaglandin R2 D-isomerase
Allergens
Pneumonia
Phenotype
Prostaglandin D2
Lung
Dependovirus
mannose receptor
Green Fluorescent Proteins
Immunoglobulin E
Down-Regulation
Asthma
Cytokines
Gene Expression
Genes

Keywords

  • asthma
  • macrophage
  • Mannose receptor
  • miR-511-3p

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Zhou, Y., Do, D. C., Ishmael, F. T., Squadrito, M. L., Tang, H. M., Tang, H. L., ... Gao, P. (2018). Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p. Journal of Allergy and Clinical Immunology, 141(1), 350-364.e8. https://doi.org/10.1016/j.jaci.2017.04.049

Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p. / Zhou, Yufeng; Do, Danh C.; Ishmael, Faoud T.; Squadrito, Mario Leonardo; Tang, Ho Man; Tang, Ho Lam; Hsu, Man Hsun; Qiu, Lipeng; Li, Changjun; Zhang, Yongqing; Becker, Kevin G.; Wan, Mei; Huang, Shau Ku; Gao, Peisong.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 1, 01.01.2018, p. 350-364.e8.

Research output: Contribution to journalArticle

Zhou, Y, Do, DC, Ishmael, FT, Squadrito, ML, Tang, HM, Tang, HL, Hsu, MH, Qiu, L, Li, C, Zhang, Y, Becker, KG, Wan, M, Huang, SK & Gao, P 2018, 'Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p', Journal of Allergy and Clinical Immunology, vol. 141, no. 1, pp. 350-364.e8. https://doi.org/10.1016/j.jaci.2017.04.049
Zhou, Yufeng ; Do, Danh C. ; Ishmael, Faoud T. ; Squadrito, Mario Leonardo ; Tang, Ho Man ; Tang, Ho Lam ; Hsu, Man Hsun ; Qiu, Lipeng ; Li, Changjun ; Zhang, Yongqing ; Becker, Kevin G. ; Wan, Mei ; Huang, Shau Ku ; Gao, Peisong. / Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 1. pp. 350-364.e8.
@article{2a05d3ffc2d742a6b54956928a0dbd7a,
title = "Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p",
abstract = "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.",
keywords = "asthma, macrophage, Mannose receptor, miR-511-3p",
author = "Yufeng Zhou and Do, {Danh C.} and Ishmael, {Faoud T.} and Squadrito, {Mario Leonardo} and Tang, {Ho Man} and Tang, {Ho Lam} and Hsu, {Man Hsun} and Lipeng Qiu and Changjun Li and Yongqing Zhang and Becker, {Kevin G.} and Mei Wan and Huang, {Shau Ku} and Peisong Gao",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.jaci.2017.04.049",
language = "English",
volume = "141",
pages = "350--364.e8",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "1",

}

TY - JOUR

T1 - Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p

AU - Zhou, Yufeng

AU - Do, Danh C.

AU - Ishmael, Faoud T.

AU - Squadrito, Mario Leonardo

AU - Tang, Ho Man

AU - Tang, Ho Lam

AU - Hsu, Man Hsun

AU - Qiu, Lipeng

AU - Li, Changjun

AU - Zhang, Yongqing

AU - Becker, Kevin G.

AU - Wan, Mei

AU - Huang, Shau Ku

AU - Gao, Peisong

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - asthma

KW - macrophage

KW - Mannose receptor

KW - miR-511-3p

UR - http://www.scopus.com/inward/record.url?scp=85023595098&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023595098&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2017.04.049

DO - 10.1016/j.jaci.2017.04.049

M3 - Article

AN - SCOPUS:85023595098

VL - 141

SP - 350-364.e8

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 1

ER -