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

Journal article


Chen, Francis M, Tse, Joyce Ky, Jin, Leigang, Chook, Chui Yiu Bamboo, Leung, Fung Ping, Tse, Gary, Woo, Connie W, Xu, Aimin, Chawla, Ajay, Tian, Xiao Yu, Chan, Ting-Fung and Wong, Wing Tak 2022. Type 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration. Theranostics. 12 (3), pp. 1161-1172. https://doi.org/10.7150/thno.67515
AuthorsChen, Francis M, Tse, Joyce Ky, Jin, Leigang, Chook, Chui Yiu Bamboo, Leung, Fung Ping, Tse, Gary, Woo, Connie W, Xu, Aimin, Chawla, Ajay, Tian, Xiao Yu, Chan, Ting-Fung and Wong, Wing Tak
Abstract Neonatal immunity is functionally immature and skewed towards a T 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. 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. Our results confirm that the T 2 cytokines: IL-4 and IL-13, which skews neonatal immunity to a T 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. [Abstract copyright: © The author(s).]
KeywordsNeonatal heart regeneration; Alternatively activated macrophages; IL-13; IL-4; TH2 immunity; Left anterior descending coronary artery ligation
Year2022
JournalTheranostics
Journal citation12 (3), pp. 1161-1172
PublisherIvyspring International Publisher
ISSN1838-7640
Digital Object Identifier (DOI)https://doi.org/10.7150/thno.67515
https://doi.org/thnov12p1161
Official URLhttps://www.thno.org/v12p1161.htm
Publication dates
Online01 Jan 2022
Publication process dates
Accepted02 Dec 2021
Deposited28 Feb 2022
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https://repository.canterbury.ac.uk/item/9087y/type-2-innate-immunity-drives-distinct-neonatal-immune-profile-conducive-for-heart-regeneration

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