PPAR and Immune System-What Do We Know?
Open accessAbstract
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear steroid receptor superfamily. Originally, the receptors were identified as critical controllers for several key enzymes that catalyze the oxidation of fatty acids. PPARs consist of three members: PPAR-alpha, PPAR-beta/delta, and PPAR-gamma. Among them, PPAR-gamma is essential for controlling thermogenesis and adipocyte differentiation. The ligands for PPAR-gamma include 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2)--a metabolite from the prostaglandin synthesis pathway, and "glitazones"--drugs utilized in the treatment of patients with diabetes. The precursors for prostaglandins are fatty acids consumed from diet and these precursors have long been postulated to have a regulatory role in immune functions. Emerging evidence indicates that PPAR-gamma and its ligands are indeed important for the modulation of immune and inflammatory reactions. In this review, we will spotlight the molecular mechanisms of receptor/ligand function and how they may regulate immune and inflammatory reactions. We also propose that PPAR-gamma and its endogenous ligands are participating factors for Type 1/Type 2 T and NK cell differentiation and development. Deciphering the mechanism of action of PPAR-gamma and its ligands may lead to a new therapeutic regiment for treatment of diseases involving dysfunction of the immune system.
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PPARs are concentrated in tissues with high metabolic demand, including the liver, kidneys, and brain, and serve as important regulators of the immune system.
“PPARs are concentrated in tissues with high metabolic demand, including the liver, kidneys, and brain, and serve as important regulators of the immune system”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Zhang and Young, 2002
Cites
Braissant, O., Foufelle, F., Scotto, C., Dauça, M., & Wahli, W. (1996) · Endocrinology · doi:10.1210/endo.137.1.8536636 · Cited by 2,217 · see citing works
Lee, H. J., Takemoto, N., Kurata, H., Kamogawa, Y., Miyatake, S., O'Garra, A., & Arai, N. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.1.105 · Cited by 393 · see citing works
The role of PPARs in inflammation and immunity
Clark, R. B. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.71.3.388 · Cited by 337 · see citing works
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Starnes, H. M., Rock, K. D., Jackson, T. W., & Belcher, S. M. (2022) · Frontiers in Toxicology · doi:10.3389/ftox.2022.881584 · Cited by 166 · see citing works
- Authors
- Zhang, X., & Young, H. A.
- Affiliations
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Zhang, Xia
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 2
- Issue
- 8
- Pages
- 1029-1044
- ISSN
- 1567-5769 (ISSN-L)
- PMC
- PMC2543934
- OpenAlex
- W2031612442
- Cited by
- 123
- References
- 3
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 9 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 6 · 2014: 2 · 2013: 2 · 2012: 5
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (Z01BC009283)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- peroxisome proliferator-activated receptors, PPARγ, PPARα, PPARδ, 15-deoxy-Δ12,14-prostaglandin J2, thiazolidinediones, immune regulation, inflammation, T cell differentiation, NK cell development, fatty acid oxidation, nuclear steroid receptors, prostaglandin synthesis
- MeSH terms
- Animals, Humans, Immune System, Transcription Factors, Signal Transduction, Receptors, Cytoplasmic and Nuclear
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