Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization
Abstract
Macrophages become activated initiating innate immune responses. Depending on the signals, macrophages obtain an array of activation phenotypes, described by the broad terms of M1 or M2 phenotype. The PI3K/Akt/mTOR pathway mediates signals from multiple receptors including insulin receptors, pathogen-associated molecular pattern receptors, cytokine receptors, adipokine receptors, and hormones. As a result, the Akt pathway converges inflammatory and metabolic signals to regulate macrophage responses modulating their activation phenotype. Akt is a family of three serine-threonine kinases, Akt1, Akt2, and Akt3. Generation of mice lacking individual Akt, PI3K, or mTOR isoforms and utilization of RNA interference technology have revealed that Akt signaling pathway components have distinct and isoform-specific roles in macrophage biology and inflammatory disease regulation, by controlling inflammatory cytokines, miRNAs, and functions including phagocytosis, autophagy, and cell metabolism. Herein, we review the current knowledge on the role of the Akt signaling pathway in macrophages, focusing on M1/M2 polarization and highlighting Akt isoform-specific functions.
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PI3K-AKT dependent MerTK activity inhibited polarization towards an M1 state.
“Specifically, PI3K-AKT dependent MerTK activity inhibited polarization towards an M1 state (79).”
From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [79]
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- Authors
- Vergadi, E., Ieronymaki, E., Lyroni, K., Vaporidi, K., & Tsatsanis, C.
- Affiliations
- University of Crete (GR)
- Corresponding author
- Vergadi, Eleni
- Ieronymaki, Eleftheria
- Lyroni, Konstantina
- Tsatsanis, Christos
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-02-01
- Volume
- 198
- Issue
- 3
- Pages
- 1006-1014
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2582393724
- Cited by
- 1,148
- References
- 8
- Citations by year
- 2026: 101 · 2025: 175 · 2024: 180 · 2023: 166 · 2022: 143 · 2021: 138 · 2020: 121 · 2019: 65 · 2018: 39 · 2017: 18 · 2013: 1
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- Akt signaling, macrophage activation, macrophage polarization, PI3K/AKT/mTOR pathway, Akt isoforms, innate immunity, inflammatory cytokines, phagocytosis, autophagy, cellular metabolism, adipokine receptors, cytokine receptors, microRNA
- MeSH terms
- Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Animals, Apolipoproteins E, Autophagy, Endotoxins, Humans, Macrophage Activation, Macrophages, Phagocytosis, Signal Transduction, Cell Polarity, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, TOR Serine-Threonine Kinases
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