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Published on: November 17, 2023
Macrophage phenotypes during tissue repair
Margaret L Novak1, Timothy J Koh
1Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
Abstract:
Mp are crucial for tissue repair and regeneration but can also contribute to tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best-characterized in vitro phenotypes are a proinflammatory "M1" phenotype, produced by exposure to IFN-γ and TNF-α, and an anti-inflammatory "M2a" phenotype, produced by IL-4 or IL-13. M2a Mp are frequently termed "wound healing" Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro-defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a-associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1- and M2-associated markers may be expressed simultaneously by actual tissue-repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.
Insights
Macrophages (Mp) are vital for tissue repair but can cause damage. This review argues that in vivo Mp phenotypes are complex and temporally regulated, challenging simple M1/M2 classifications for better healing therapies.
Area of Science:
- Immunology
- Cell Biology
- Regenerative Medicine
Background:
- Macrophages (Mp) play dual roles in tissue repair, promoting healing or causing damage and fibrosis.
- In vitro studies define proinflammatory (M1) and anti-inflammatory (M2a) Mp phenotypes based on specific stimuli.
- M2a Mp are often associated with wound healing due to their reparative factor expression.
Purpose of the Study:
- To review current knowledge of macrophage phenotypes during tissue repair.
- To challenge the applicability of in vitro-defined M1 and M2 phenotypes to in vivo tissue repair contexts.
- To highlight the heterogeneity and temporal regulation of Mp populations in vivo.
Main Methods:
- Review of existing literature on macrophage phenotypes in tissue repair.
- Analysis of in vitro M1 and M2 definitions and their limitations.
- Comparison of in vitro findings with in vivo observations of Mp behavior during repair.
Main Results:
- In vivo Mp populations are heterogeneous and temporally regulated, not fitting simple M1 or M2 categories.
- Early-stage repair Mp show more proinflammatory characteristics than later-stage Mp.
- Phenotypic markers can be independently expressed in vivo, and M1/M2 markers can co-exist in tissue-repair Mp.
Conclusions:
- In vivo macrophage behavior during tissue repair is more complex than in vitro models suggest.
- Existing M1/M2 classifications are insufficient to describe the dynamic Mp populations in healing tissues.
- Understanding these complex Mp phenotypes is crucial for developing novel therapeutic strategies to enhance healing.
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