PPARγ LIGAND SUPPRESSES FOXP3 EXPRESSION IN T-REGULATORY CELLS DURING EXCESSIVE INFLAMMATION VIA MODULATING HISTONE ACETYLTRANSFERASE AND HDAC6/11 ACTIVITIES

Received 2022-06-15; Accepted 2022-09-10; Published 2022-12-31

Authors

  • Nor Effa Syazuli Zulkafli Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Bertam, Kepala Batas, Penang, Malaysia.
  • Lee Pei Chen Complex E, Centre for Administration Federal Government, Ministry of Health, Malaysia, 62590, Putrajaya, Malaysia.
  • Norazmi Mohd Nor School of Health Sciences, Universiti Sains Malaysia, Health Campus, 12150 Kubang Kerian, Kelantan, Malaysia.

DOI:

https://doi.org/10.22452/jummec.sp2022no1.7

Abstract

Natural T-Regulatory (nTreg) cells represent approximately 8-10% of the total CD4+ T cell population and constantly expressing Foxp3 proteins. These cells are crucial for immune homeostasis, preventing over-inflammation and autoimmunity. Our previous study reported that PPARγ ligand, 15d-PGJ2 negatively influences the expression of Foxp3 in nTreg cells, which reflexes the attenuation in immunosuppressive function of nTreg cells. This study aims to unveil the molecular mechanism of Foxp3 suppression by PPARγ in nTreg cells during autoimmune Type 1 Diabetes. Co-stimulatory proteins were measured using flow cytometry and methylation measurement of Foxp3 expression was measured based on histone modification activity. Nuclear proteins of isolated cells were extracted out to measure two HDAC and two HAT enzyme activities using ELISA. Purified nTreg cells were isolated using MoFlow Cell sorter, and will be then cultured for 72 hrs to mimic the TCR activation and downstream signalling. The expression of Foxp3 in these cells were measured using flow cytometry analysis and were positively selected. Current data showed that histone acetylation activities were cross talked with PPARγ pathway in nTreg cells from diabetic, but in healthy mice. FoxP3 gene expression may be regulated via histone modification that in diabetic mice via PPARγ- independent pathways. Altogether, this study provides fundamental analysis on the putative role of PPARγ ligand 15d-PGJ2 as HDAC6/11 inhibitors. Therefore, this may suggest that combination of 15d-PGJ2 and GW9662 can be an alternative to HDAC6 inhibitor which is less toxic compared to pan-HDACi in treating inflammatory-related diseases. These ligands also potentially able to suppress the microenvironment of nTreg cells protecting tumour-bearing cells.

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Globally, the prevalence of both communicable and non-communicable diseases has reached pandemic levels. The prevalence of diseases including type 2 diabetes, hypertension, and obesity is worldwide. With the help of technology, many of the most severe infectious diseases of the 20th century may now be fought. These disorders are conditions that develop over an extended period of time as a result of a combination of genetic, physiological, environmental, and behavioural factors, especially the non-communicable diseases. The goal of this Special Issue, "Combating disease: Current trends, risk, treatment and prevention" is to discuss a wide range of disease-related topics, including make studies about the current pandemic season public. We specially encourage articles that offer fresh perspectives on medicine, medical systems, and management including epidemiological studies, basic science of local and systemic responses related to the medical sciences, fundamental research in medical sciences in lowering risk, improving treatment and prevention. All Special issues of JUMMEC follow the exact peer review process as regular papers and are published along with the regular issues of the journal when they are accepted. There are additionally labelled as belonging to a Special Issue and share a particular topic of interest to the scientific community.

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Published

2022-12-31

Issue

Special Issue 1 (2022) Combating disease: Current trends, risk, treatment and prevention

Section

Research article

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