Faculty Collaboration Database

IL-13 promotes functional recovery after myocardial infarction via direct signaling to macrophages. JCI Insight 2024 Jan 23;9(2)

Date

12/06/2023

Pubmed ID

38051583

Pubmed Central ID

PMC10906228

DOI

10.1172/jci.insight.172702

Scopus ID

2-s2.0-85183312687 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

There is great interest in identifying signaling pathways that promote cardiac repair after myocardial infarction (MI). Prior studies suggest a beneficial role for IL-13 signaling in neonatal heart regeneration; however, the cell types mediating cardiac regeneration and the extent of IL-13 signaling in the adult heart after injury are unknown. We identified an abundant source of IL-13 and the related cytokine, IL-4, in neonatal cardiac type 2 innate lymphoid cells, but this phenomenon declined precipitously in adult hearts. Moreover, IL-13 receptor deletion in macrophages impaired cardiac function and resulted in larger scars early after neonatal MI. By using a combination of recombinant IL-13 administration and cell-specific IL-13 receptor genetic deletion models, we found that IL-13 signaling specifically to macrophages mediated cardiac functional recovery after MI in adult mice. Single transcriptomics revealed a subpopulation of cardiac macrophages in response to IL-13 administration. These IL-13-induced macrophages were highly efferocytotic and were identified by high IL-1R2 expression. Collectively, we elucidated a strongly proreparative role for IL-13 signaling directly to macrophages following cardiac injury. While this pathway is active in proregenerative neonatal stages, reactivation of macrophage IL-13 signaling is required to promote cardiac functional recovery in adults.

Author List

Alvarez-Argote S, Paddock SJ, Flinn MA, Moreno CW, Knas MC, Almeida VA, Buday SL, Bakhshian Nik A, Patterson M, Chen YG, Lin CW, O'Meara CC

Authors

Amirala Bakhshiannik Postdoctoral Fellow in the Physiology department at Medical College of Wisconsin
Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Michael Andrew Flinn Postdoctoral Fellow in the Physiology department at Medical College of Wisconsin
Chien-Wei Lin PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Immunity, Innate
Interleukin-13
Lymphocytes
Macrophages
Mice
Myocardial Infarction
Receptors, Interleukin-13