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

doi:10.1016/j.jaci.2017.04.049

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 T_H2/T_H17 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 language	English (US)
Pages (from-to)	350-364.e8
Journal	Journal of Allergy and Clinical Immunology
Volume	141
Issue number	1
DOIs	https://doi.org/10.1016/j.jaci.2017.04.049
State	Published - Jan 2018

Keywords

Mannose receptor
asthma
macrophage
miR-511-3p

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.jaci.2017.04.049

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Zhou, Y., Do, D. C., Ishmael, F. T., Squadrito, M. L., Tang, H. M., Tang, H. L., Hsu, M. H., Qiu, L., Li, C., Zhang, Y., Becker, K. G., Wan, M., Huang, S. K., & 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

@article{54868d4fbd3d497bbebf2b35ba7cf96d,

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 = "Mannose receptor, asthma, macrophage, 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",

note = "Funding Information: Supported by grants from the US National Institutes of Health (NIH; RO1ES021739, R21 AI109062, and R21 AI121768) and the National Science Foundation of China (NSFC; 81628001; to P.G.); the Intramural Research Program of the National Institutes of Health, National Institute on Aging; the China 1000 Young Talents Plan Program (to Y.Z.); and Fudan Children's Hospital and Fudan University for Initial Funding, NSFC 81671561, and MOST 2016YFC1305102 (to Y.Z.); and by grants from the National Health Research Institutes (EOPP10-014 and EOSP07-014 to S.-K.H.) and the Ministry of Health (EODOH01; to S.-K.H.); Academia Sinica (AS-105-TP-B05 to SK Huang); and Kaohsiung Medical University “Aim for the Top Universities Grant” and “the Talent Plan” (KMU-TP-105A04 and KMU-SH000184 to SK Huang), Taiwan. Publisher Copyright: {\textcopyright} 2017 American Academy of Allergy, Asthma & Immunology",

year = "2018",

month = jan,

doi = "10.1016/j.jaci.2017.04.049",

language = "English (US)",

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

N1 - Funding Information: Supported by grants from the US National Institutes of Health (NIH; RO1ES021739, R21 AI109062, and R21 AI121768) and the National Science Foundation of China (NSFC; 81628001; to P.G.); the Intramural Research Program of the National Institutes of Health, National Institute on Aging; the China 1000 Young Talents Plan Program (to Y.Z.); and Fudan Children's Hospital and Fudan University for Initial Funding, NSFC 81671561, and MOST 2016YFC1305102 (to Y.Z.); and by grants from the National Health Research Institutes (EOPP10-014 and EOSP07-014 to S.-K.H.) and the Ministry of Health (EODOH01; to S.-K.H.); Academia Sinica (AS-105-TP-B05 to SK Huang); and Kaohsiung Medical University “Aim for the Top Universities Grant” and “the Talent Plan” (KMU-TP-105A04 and KMU-SH000184 to SK Huang), Taiwan. Publisher Copyright: © 2017 American Academy of Allergy, Asthma & Immunology

PY - 2018/1

Y1 - 2018/1

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 - Mannose receptor

KW - asthma

KW - macrophage

KW - miR-511-3p

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SP - 350-364.e8

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ER -

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

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