| Presentation preference | Poster presentation |
| Title | TET2-mediated upregulation of 5-hydroxymethylcytosine in LRRC39 promoter promotes Th1 responses in Vogt-Koyanagi-Harada disease |
| Purpose | To depict the genome-wide DNA 5-hmC and transcription profile and uncover aberrant hydroxymethylation modifications axis in VKH disease. |
| Methods | The 5-hmC-Seal-seq and RNA-seq were performed to uncover differential DNA5-hmC and transcription pattern. The global DNA 5-hmC level, TET activity, expression of TET family and differential hydroxymethylated genes, frequencies of Th1 cell and productions of Th-related cytokines in CD4+ T cells were detected. |
| Results | The global DNA 5-hmC level and the TET activity were elevated in association with the up-regulated expression of TET1 and TET2 in CD4+T cells from active VKH patients compared to healthy controls. A combined analysis of sequencing results showed that a total of 6 crucial genes were identified in CD4+T cells between active VKH patients and normal controls. The promoter 5-hmC and mRNA levels of leucine rich repeat containing 39 (LRRC39) were verified to be elevated in active VKH patients. Functional experiments showed that TET2 could up-regulate LRRC39 mRNA expression by increasing the promoter 5-hmC level of LRRC39 in active VKH CD4+ T cells. Up-regulated LRRC39 expression could not only increase the frequencies of IFN-γ+ CD4+ T cells as well as the secretions of IFN-γ. |
| Conclusion | This study reveals a novel axis, TET2–5-hmC-LRRC39–Th1 responses axis, in the pathogenesis of VKH disease and provides a potential target for further investigation into the prevention and treatment of this disease. |
| Conflict of interest | No |
Authors 1
| Last name | ZHANG |
| Initials of first name(s) | WY |
| Department | The First Affiliated Hospital of Chongqing Medical University |
| City | Chongqing |
| Country | China |
Authors 2
| Last name | YANG |
| Initials of first name(s) | PZ |
| Department | The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmo |
| City | Chongqing |
| Country | China |
