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The Impact of Versatile Macrophage Functions on Acute Kidney Injury and Its Outcomes
1Research & Early Development, Biogen Inc., Cambridge, MA, United States.
Abstract:
Acute kidney injury (AKI) is a common and devastating clinical condition with a high morbidity and mortality rate and is associated with a rapid decline of kidney function mostly resulting from the injury of proximal tubules. AKI is typically accompanied by inflammation and immune activation and involves macrophages (Mϕ) from the beginning: The inflamed kidney recruits "classically" activated (M1) Mϕ, which are initially poised to destroy potential pathogens, exacerbating inflammation. Of note, they soon turn into "alternatively" activated (M2) Mϕ and promote immunosuppression and tissue regeneration. Based on their roles in kidney recovery, there is a growing interest to use M2 Mϕ and Mϕ-modulating agents therapeutically against AKI. However, it is pertinent to note that the clinical translation of Mϕ-based therapies needs to be critically reviewed and questioned since Mϕ are functionally plastic with versatile roles in AKI and some Mϕ functions are detrimental to the kidney during AKI. In this review, we discuss the current state of knowledge on the biology of different Mϕ subtypes during AKI and, especially, on their role in AKI and assess the impact of versatile Mϕ functions on AKI based on the findings from translational AKI studies.
Insights
Macrophages play a dual role in acute kidney injury (AKI). While M2 macrophages aid kidney recovery, their versatile functions and plasticity necessitate careful consideration for therapeutic strategies targeting AKI.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Acute kidney injury (AKI) is a severe condition characterized by rapid kidney function decline, often due to proximal tubule injury.
- Inflammation and immune cell involvement, particularly macrophages (Mϕ), are central to AKI pathogenesis.
- Macrophages exhibit plasticity, transitioning from pro-inflammatory M1 to immunosuppressive/regenerative M2 phenotypes.
Purpose of the Study:
- To review the current understanding of macrophage biology in AKI.
- To analyze the distinct roles of Mϕ subtypes in kidney injury and recovery.
- To assess the impact of macrophage plasticity on AKI outcomes and therapeutic potential.
Main Methods:
- Literature review of current knowledge on Mϕ subtypes in AKI.
- Analysis of findings from translational AKI studies.
- Assessment of macrophage functional versatility in the context of AKI.
Main Results:
- M1 macrophages exacerbate inflammation in AKI, while M2 macrophages are implicated in tissue repair.
- Macrophage plasticity presents both beneficial and detrimental functions in AKI.
- Translational studies highlight the complex impact of Mϕ on AKI progression and recovery.
Conclusions:
- Therapeutic strategies targeting macrophages for AKI require critical evaluation due to their complex and context-dependent roles.
- Understanding Mϕ plasticity is crucial for developing effective AKI treatments.
- Further research is needed to harness the regenerative potential of M2 macrophages while mitigating detrimental Mϕ functions in AKI.
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