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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
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IL-17A Orchestrates Reactive Oxygen Species/HIF1α-Mediated Metabolic Reprogramming in Psoriasis.
Bhavuk Dhamija1, Soumitra Marathe1, Vinanti Sawant1
1Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Journal of Immunology (Baltimore, Md. : 1950)
|November 29, 2023
Summary
Interleukin-17A (IL-17A) drives metabolic changes in skin keratinocytes, promoting their proliferation. Targeting these metabolic pathways could offer new treatments for psoriasis.
Area of Science:
- Dermatology
- Immunology
- Metabolic Biology
Background:
- Psoriasis is an immunometabolic disorder where IL-17A is a key pathogenic cytokine.
- IL-17A's role in cutaneous immune cells is known, but its effects on nonimmune skin cells like keratinocytes are less understood.
Purpose of the Study:
- To investigate the functional and metabolic effects of IL-17A on human primary keratinocytes (HPKs).
- To uncover IL-17A's role in metabolic reprogramming of keratinocytes.
Main Methods:
- Multiomics profiling (proteomics, metabolomics) and systems biology (MitoCore modeling).
- Biochemical assays and stable isotope-resolved metabolomics to validate metabolic changes.
- Investigated downstream effects including reactive oxygen species (ROS) and HIF1α.
Main Results:
- IL-17A significantly reprogrammed HPK metabolism, increasing glycolysis, glutaminolysis, and lipid uptake.
- IL-17A triggered mitochondrial ROS and HIF1α, leading to keratinocyte proliferation.
- These IL-17A-induced changes mirrored those found in psoriatic skin.
Conclusions:
- Keratinocytes are key targets of IL-17A in the skin.
- IL-17A induces metabolic reprogramming in keratinocytes, contributing to hyperproliferation.
- Inhibiting HIF1α or ROS reversed IL-17A-mediated metabolic changes and proliferation, suggesting therapeutic potential.
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