Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants.

Lao, JC; Bui, CB; Pang, MA; Cho, SX; Rudloff, I; Elgass, K; Schröder, J; Maksimenko, A; Mangan, NE; Starkey, MR; Skuza, EM; Sun, YBY; Beker, F; Collins, CL; Kamlin, OF; König, K; Malhotra, A; Tan, K; Theda, C; Young, MJ; McLean, CA; Wilson, NJ; Sehgal, A; Hansbro, PM; Pearson, JT; Polo, JM; Veldman, A; Berger, PJ; Nold-Petry, CA; Nold, MF

Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants.

Lao, JC Bui, CB Pang, MA Cho, SX Rudloff, I Elgass, K Schröder, J Maksimenko, A Mangan, NE Starkey, MR Skuza, EM Sun, YBY Beker, F Collins, CL Kamlin, OF König, K Malhotra, A Tan, K Theda, C Young, MJ McLean, CA Wilson, NJ Sehgal, A Hansbro, PM Pearson, JT Polo, JM Veldman, A Berger, PJ Nold-Petry, CA Nold, MF

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Publisher:: AMER ASSOC ADVANCEMENT SCIENCE
Publication Type:: Journal Article
Citation:: Sci Transl Med, 2022, 14, (639), pp. eaaz8454
Issue Date:: 2022-04-06

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Field	Value	Language
dc.contributor.author	Lao, JC
dc.contributor.author	Bui, CB
dc.contributor.author	Pang, MA
dc.contributor.author	Cho, SX
dc.contributor.author	Rudloff, I
dc.contributor.author	Elgass, K
dc.contributor.author	Schröder, J
dc.contributor.author	Maksimenko, A
dc.contributor.author	Mangan, NE
dc.contributor.author	Starkey, MR
dc.contributor.author	Skuza, EM
dc.contributor.author	Sun, YBY
dc.contributor.author	Beker, F
dc.contributor.author	Collins, CL
dc.contributor.author	Kamlin, OF
dc.contributor.author	König, K
dc.contributor.author	Malhotra, A
dc.contributor.author	Tan, K
dc.contributor.author	Theda, C
dc.contributor.author	Young, MJ
dc.contributor.author	McLean, CA
dc.contributor.author	Wilson, NJ
dc.contributor.author	Sehgal, A
dc.contributor.author	Hansbro, PM
dc.contributor.author	Pearson, JT
dc.contributor.author	Polo, JM
dc.contributor.author	Veldman, A
dc.contributor.author	Berger, PJ
dc.contributor.author	Nold-Petry, CA
dc.contributor.author	Nold, MF
dc.date.accessioned	2023-05-18T01:15:18Z
dc.date.available	2023-05-18T01:15:18Z
dc.date.issued	2022-04-06
dc.identifier.citation	Sci Transl Med, 2022, 14, (639), pp. eaaz8454
dc.identifier.issn	1946-6234
dc.identifier.issn	1946-6242
dc.identifier.uri	http://hdl.handle.net/10453/170366
dc.description.abstract	Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3+CD4+ T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER ASSOC ADVANCEMENT SCIENCE
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1175134
dc.relation.ispartof	Sci Transl Med
dc.relation.isbasedon	10.1126/scitranslmed.aaz8454
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	06 Biological Sciences, 11 Medical and Health Sciences
dc.subject.mesh	Animals
dc.subject.mesh	Bronchopulmonary Dysplasia
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Infant, Newborn
dc.subject.mesh	Infant, Premature
dc.subject.mesh	Inflammation
dc.subject.mesh	Interleukin-13
dc.subject.mesh	Lung
dc.subject.mesh	Mice
dc.subject.mesh	Pregnancy
dc.subject.mesh	Lung
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Bronchopulmonary Dysplasia
dc.subject.mesh	Inflammation
dc.subject.mesh	Interleukin-13
dc.subject.mesh	Pregnancy
dc.subject.mesh	Infant, Newborn
dc.subject.mesh	Infant, Premature
dc.subject.mesh	Female
dc.subject.mesh	Animals
dc.subject.mesh	Bronchopulmonary Dysplasia
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Infant, Newborn
dc.subject.mesh	Infant, Premature
dc.subject.mesh	Inflammation
dc.subject.mesh	Interleukin-13
dc.subject.mesh	Lung
dc.subject.mesh	Mice
dc.subject.mesh	Pregnancy
dc.title	Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	United States
utslib.for	06 Biological Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	closed_access	*
dc.date.updated	2023-05-18T01:15:15Z
pubs.issue	639
pubs.publication-status	Published
pubs.volume	14
utslib.citation.issue	639

Abstract:

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3+CD4+ T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1β and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/170366