Next Article in Journal
Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis
Previous Article in Journal
Dietary Nitrate from Beetroot Juice for Hypertension: A Systematic Review
Article Menu
Issue 4 (December) cover image

Export Article

Open AccessArticle
Biomolecules 2018, 8(4), 135; https://doi.org/10.3390/biom8040135

Crosstalk between PPARγ Ligands and Inflammatory-Related Pathways in Natural T-Regulatory Cells from Type 1 Diabetes Mouse Model

1
School of Health Sciences, Universiti Sains Malaysia, Kelantan, Kubang Kerian 16150, Malaysia
2
Regenerative Medicine Cluster, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Bertam, Kepala Batas 13200, Malaysia
3
School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Kubang Kerian 16150, Malaysia
*
Authors to whom correspondence should be addressed.
Received: 21 June 2018 / Revised: 24 August 2018 / Accepted: 28 August 2018 / Published: 5 November 2018
Full-Text   |   PDF [4693 KB, uploaded 6 November 2018]   |  

Abstract

Immunomodulation, as a means of immunotherapy, has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulators used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e., thiazolidinedione (TZD) class of drugs on Forkhead Box P3 (Foxp3) expression and possible crosstalk between PPARγ and nTreg cells of Non-Obese Diabetes (NOD) and Non-Obese Diabetes Resistant (NOR) mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independent mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress Foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies. The co-lateral use of PPARγ ligands in nTreg cells in inducing tolerance towards pseudo-self antigens as in tumor microenvironment may uphold beneficial outcomes. View Full-Text
Keywords: T-Regulatory cells; immune regulation; Foxp3; PPARγ; autoimmune diabetes; NOD mouse; thiazolidinediones; ciglitazone; immunomodulator T-Regulatory cells; immune regulation; Foxp3; PPARγ; autoimmune diabetes; NOD mouse; thiazolidinediones; ciglitazone; immunomodulator
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Nor Effa, S.Z.; Yaacob, N.S.; Mohd Nor, N. Crosstalk between PPARγ Ligands and Inflammatory-Related Pathways in Natural T-Regulatory Cells from Type 1 Diabetes Mouse Model. Biomolecules 2018, 8, 135.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top