Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

CROSSTALK BETWEEN PPARγ LIGANDS AND INFLAMMATORY-RELATED PATHWAYS IN NATURAL T-REGULATORY CELLS FROM TYPE 1 DIABETES MOUSE MODEL

Version 1 : Received: 21 June 2018 / Approved: 22 June 2018 / Online: 22 June 2018 (09:33:32 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Abstract

Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator 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 Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and 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-independant 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.

Keywords

T-regulatory cells, immune regulation, Foxp3, PPARγ, autoimmune diabetes, NOD mouse, Thiazolidinediones, ciglitazone.

Subject

Biology and Life Sciences, Immunology and Microbiology

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