Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration

Nikolas Giannakis, Brian E. Sansbury, Andreas Patsalos, Tristan T. Hays, Colin O. Riley, Xianlin Han, Matthew Spite, L. Nagy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry–based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. These time-dependent profiles were recapitulated in sorted neutrophils and Ly6C hi and Ly6C lo muscle-infiltrating macrophages, with a distinct pro-resolving signature observed in Ly6C lo macrophages. RNA sequencing of macrophages stimulated with resolvin D2 showed similarities to transcriptional changes found during the temporal transition from Ly6C hi macrophage to Ly6C lo macrophage. In vivo, resolvin D2 increased Ly6C lo macrophages and functional improvement of the regenerating muscle. These results reveal dynamic lipid mediator signatures of innate immune cells and provide a proof of concept for their exploitable effector roles in muscle regeneration.

Original languageEnglish
Pages (from-to)626-636
Number of pages11
JournalNature Immunology
Volume20
Issue number5
DOIs
Publication statusPublished - May 1 2019

Fingerprint

Regeneration
Macrophages
Lipids
Muscles
Lipoxins
Glycerophospholipids
RNA Sequence Analysis
Leukotrienes
Ibuprofen
Prostaglandins
Skeletal Muscle
Neutrophils
Inflammation
Wounds and Injuries
resolvin D2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration. / Giannakis, Nikolas; Sansbury, Brian E.; Patsalos, Andreas; Hays, Tristan T.; Riley, Colin O.; Han, Xianlin; Spite, Matthew; Nagy, L.

In: Nature Immunology, Vol. 20, No. 5, 01.05.2019, p. 626-636.

Research output: Contribution to journalArticle

Giannakis, N, Sansbury, BE, Patsalos, A, Hays, TT, Riley, CO, Han, X, Spite, M & Nagy, L 2019, 'Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration', Nature Immunology, vol. 20, no. 5, pp. 626-636. https://doi.org/10.1038/s41590-019-0356-7
Giannakis, Nikolas ; Sansbury, Brian E. ; Patsalos, Andreas ; Hays, Tristan T. ; Riley, Colin O. ; Han, Xianlin ; Spite, Matthew ; Nagy, L. / Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration. In: Nature Immunology. 2019 ; Vol. 20, No. 5. pp. 626-636.
@article{04f2c51100f1485aa0ca8ee253f613b3,
title = "Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration",
abstract = "Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry–based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. These time-dependent profiles were recapitulated in sorted neutrophils and Ly6C hi and Ly6C lo muscle-infiltrating macrophages, with a distinct pro-resolving signature observed in Ly6C lo macrophages. RNA sequencing of macrophages stimulated with resolvin D2 showed similarities to transcriptional changes found during the temporal transition from Ly6C hi macrophage to Ly6C lo macrophage. In vivo, resolvin D2 increased Ly6C lo macrophages and functional improvement of the regenerating muscle. These results reveal dynamic lipid mediator signatures of innate immune cells and provide a proof of concept for their exploitable effector roles in muscle regeneration.",
author = "Nikolas Giannakis and Sansbury, {Brian E.} and Andreas Patsalos and Hays, {Tristan T.} and Riley, {Colin O.} and Xianlin Han and Matthew Spite and L. Nagy",
year = "2019",
month = "5",
day = "1",
doi = "10.1038/s41590-019-0356-7",
language = "English",
volume = "20",
pages = "626--636",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration

AU - Giannakis, Nikolas

AU - Sansbury, Brian E.

AU - Patsalos, Andreas

AU - Hays, Tristan T.

AU - Riley, Colin O.

AU - Han, Xianlin

AU - Spite, Matthew

AU - Nagy, L.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry–based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. These time-dependent profiles were recapitulated in sorted neutrophils and Ly6C hi and Ly6C lo muscle-infiltrating macrophages, with a distinct pro-resolving signature observed in Ly6C lo macrophages. RNA sequencing of macrophages stimulated with resolvin D2 showed similarities to transcriptional changes found during the temporal transition from Ly6C hi macrophage to Ly6C lo macrophage. In vivo, resolvin D2 increased Ly6C lo macrophages and functional improvement of the regenerating muscle. These results reveal dynamic lipid mediator signatures of innate immune cells and provide a proof of concept for their exploitable effector roles in muscle regeneration.

AB - Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry–based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. These time-dependent profiles were recapitulated in sorted neutrophils and Ly6C hi and Ly6C lo muscle-infiltrating macrophages, with a distinct pro-resolving signature observed in Ly6C lo macrophages. RNA sequencing of macrophages stimulated with resolvin D2 showed similarities to transcriptional changes found during the temporal transition from Ly6C hi macrophage to Ly6C lo macrophage. In vivo, resolvin D2 increased Ly6C lo macrophages and functional improvement of the regenerating muscle. These results reveal dynamic lipid mediator signatures of innate immune cells and provide a proof of concept for their exploitable effector roles in muscle regeneration.

UR - http://www.scopus.com/inward/record.url?scp=85063767805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063767805&partnerID=8YFLogxK

U2 - 10.1038/s41590-019-0356-7

DO - 10.1038/s41590-019-0356-7

M3 - Article

VL - 20

SP - 626

EP - 636

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 5

ER -