Genome-Wide DNA Methylation Profiling in CD8 T-Cells and Gamma Delta T-Cells of Asian Indian Patients With Takayasu Arteritis

Jayakanthan Kabeerdoss; Debashish Danda; Ruchika Goel; Hindhumathi Mohan; Sumita Danda; R Hal Scofield

doi:10.3389/fcell.2022.843413

Genome-Wide DNA Methylation Profiling in CD8 T-Cells and Gamma Delta T-Cells of Asian Indian Patients With Takayasu Arteritis

Front Cell Dev Biol. 2022 Jun 23:10:843413. doi: 10.3389/fcell.2022.843413. eCollection 2022.

Authors

Jayakanthan Kabeerdoss^{1

2}, Debashish Danda¹, Ruchika Goel¹, Hindhumathi Mohan¹, Sumita Danda³, R Hal Scofield^{4

5}

Affiliations

¹ Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India.
² Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
³ Department of Medical Genetics, Christian Medical College, Vellore, India.
⁴ Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
⁵ Department of Veterans Affairs, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.

Abstract

Background: Takayasu's Arteritis (TA) is a chronic inflammatory disease that affects aorta and its main branches at their origin. Genetic, pathological and functional studies have shown that CD8 and Gamma delta (γ/δ) T-lymphocytes are involved in inflammatory processes in affected regions of arteries causing vascular damage. The molecular function of these lymphocytes remains unclear and currently no epigenetic studies are available in TA. We primarily performed genome wide methylation analysis in CD8 T cells and γδ T cells of patients with TA and compared with healthy controls. Methods: We recruited 12 subjects in each group namely TA patient and healthy controls. Blood samples were collected after obtaining informed written consent. CD8 T cells and γδ T cells were separated from whole blood. DNA extracted from these cells and were subjected to bisulfite treatment. Finally, bisulfite treated DNA was loaded in Infinium Methylation EPIC array. Bioinformatics analysis was used to identify differential methylation regions which were then mapped to genes. Results: Interleukin (IL)-32 and Lymphotoxin-A were genes significantly hypomethylated in CD8 T-cells. Anti-inflammatory cytokine genes, IL-10, IL-1RN and IL-27 were hypomethylated in γδ T cells of TA patients as compared to healthy controls. Gene enrichment analysis using Gene Ontology (GO) database and Kyoto Encyclopaedia of Genes and Genomes (KEGG) identified that genes involved in T-cell receptor signalling pathways were hypomethylated in CD8 T-cells and hypermethylated in γδ T cells of TA patients. Conclusion: CD8 T-cells might play a major role in immunopathogenesis of inflammation in TA, whereas γδ T cells may play a regulatory role.

Keywords: DNA methylation; Interleukin-32; Takayasu’s arteritis; epigenetics; large vessel vasculitis.