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Article: Type 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration.

TitleType 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration.
Authors
KeywordsAlternatively activated macrophages
IL-13
IL-4
Left anterior descending coronary artery ligation
Neonatal heart regeneration
TH2 immunity
Issue Date1-Jan-2022
PublisherIvyspring International Publisher
Citation
Theranostics, 2022, v. 12, n. 3, p. 1161-1172 How to Cite?
AbstractAims: Neonatal immunity is functionally immature and skewed towards a TH2-driven, anti-inflammatory profile. This neonatal immunotolerance is partly driven by the type 2 cytokines: interleukin-4 (IL-4) and interleukin-13 (IL-13). Studies on neonatal cardiac regeneration reveal the beneficial role of an anti-inflammatory response in restoring cardiac function after injury. However, the role of an imbalanced immune repertoire observed in neonates on tissue regeneration is poorly understood; specifically, whether IL-4 and IL-13 actively modulate neonatal immunity during cardiac injury. Methods and results: Neonatal mice lacking IL-4 and IL-13 (DKOs) examined at 2 days after birth exhibited reduced anti-inflammatory immune populations with basal cardiac immune populations like adult mice. Examination of neonates lacking IL-4 and IL-13 at 2 days post cardiac ischemic injury, induced on the second day after birth, showed impaired cardiac function compared to their control counterparts. Treatment with either IL-4 or IL-13 cytokine during injury restored both cardiac function and immune population profiles in knockout mice. Examination of IL-4/IL-13 downstream pathways revealed the role of STAT6 in mediating the regenerative response in neonatal hearts. As IL-4/IL-13 drives polarization of alternatively activated macrophages, we also examined the role of IL-4/IL-13 signaling within the myeloid compartment during neonatal cardiac regeneration. Injury of IL-4Rα myeloid specific knockout neonates 2 days after birth revealed that loss of IL-4/IL-13 signaling in macrophages alone was sufficient to impair cardiac regeneration. Conclusions: Our results confirm that the TH2 cytokines: IL-4 and IL-13, which skews neonatal immunity to a TH2 profile, are necessary for maintaining and mediating an anti-inflammatory response in the neonatal heart, in part through the activation of alternatively activated macrophages, thereby permitting a niche conducive for regeneration.
Persistent Identifierhttp://hdl.handle.net/10722/338288
ISSN
2023 Impact Factor: 12.4
2023 SCImago Journal Rankings: 2.912
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, FM-
dc.contributor.authorTse, JK-
dc.contributor.authorJin, L-
dc.contributor.authorChook, CYB-
dc.contributor.authorLeung, FP-
dc.contributor.authorTse, G-
dc.contributor.authorWoo, CW-
dc.contributor.authorXu, A-
dc.contributor.authorChawla, A-
dc.contributor.authorTian, XY-
dc.contributor.authorChan, TF-
dc.contributor.authorWong, WT-
dc.date.accessioned2024-03-11T10:27:44Z-
dc.date.available2024-03-11T10:27:44Z-
dc.date.issued2022-01-01-
dc.identifier.citationTheranostics, 2022, v. 12, n. 3, p. 1161-1172-
dc.identifier.issn1838-7640-
dc.identifier.urihttp://hdl.handle.net/10722/338288-
dc.description.abstract<b>Aims:</b> Neonatal immunity is functionally immature and skewed towards a T<sub>H</sub>2-driven, anti-inflammatory profile. This neonatal immunotolerance is partly driven by the type 2 cytokines: interleukin-4 (IL-4) and interleukin-13 (IL-13). Studies on neonatal cardiac regeneration reveal the beneficial role of an anti-inflammatory response in restoring cardiac function after injury. However, the role of an imbalanced immune repertoire observed in neonates on tissue regeneration is poorly understood; specifically, whether IL-4 and IL-13 actively modulate neonatal immunity during cardiac injury. <b>Methods and results:</b> Neonatal mice lacking IL-4 and IL-13 (DKOs) examined at 2 days after birth exhibited reduced anti-inflammatory immune populations with basal cardiac immune populations like adult mice. Examination of neonates lacking IL-4 and IL-13 at 2 days post cardiac ischemic injury, induced on the second day after birth, showed impaired cardiac function compared to their control counterparts. Treatment with either IL-4 or IL-13 cytokine during injury restored both cardiac function and immune population profiles in knockout mice. Examination of IL-4/IL-13 downstream pathways revealed the role of STAT6 in mediating the regenerative response in neonatal hearts. As IL-4/IL-13 drives polarization of alternatively activated macrophages, we also examined the role of IL-4/IL-13 signaling within the myeloid compartment during neonatal cardiac regeneration. Injury of IL-4Rα myeloid specific knockout neonates 2 days after birth revealed that loss of IL-4/IL-13 signaling in macrophages alone was sufficient to impair cardiac regeneration. <b>Conclusions:</b> Our results confirm that the T<sub>H</sub>2 cytokines: IL-4 and IL-13, which skews neonatal immunity to a T<sub>H</sub>2 profile, are necessary for maintaining and mediating an anti-inflammatory response in the neonatal heart, in part through the activation of alternatively activated macrophages, thereby permitting a niche conducive for regeneration.-
dc.languageeng-
dc.publisherIvyspring International Publisher-
dc.relation.ispartofTheranostics-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAlternatively activated macrophages-
dc.subjectIL-13-
dc.subjectIL-4-
dc.subjectLeft anterior descending coronary artery ligation-
dc.subjectNeonatal heart regeneration-
dc.subjectTH2 immunity-
dc.titleType 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration.-
dc.typeArticle-
dc.identifier.doi10.7150/thno.67515-
dc.identifier.pmid35154480-
dc.identifier.scopuseid_2-s2.0-85121913691-
dc.identifier.volume12-
dc.identifier.issue3-
dc.identifier.spage1161-
dc.identifier.epage1172-
dc.identifier.eissn1838-7640-
dc.identifier.isiWOS:000744097800004-
dc.identifier.issnl1838-7640-

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