Different epigenome regulation and transcriptome expression of CD4+ and CD8+ T cells from monozygotic twins discordant for psoriasis

Australas J Dermatol. 2020 Nov;61(4):e388-e394. doi: 10.1111/ajd.13325. Epub 2020 May 21.

Abstract

Objectives: Psoriasis is an immunodeficient skin disorder, and its exact pathogenesis is unclear. Monozygotic twins are presumed to be genetically identical, and their phenotypic differences may be due to transcriptional regulation or epigenome factors. To explain the inconsistency between twins, we have collected 3 pairs of monozygotic twins who are discordant for psoriasis.

Methods: Reduced representation of bisulfite sequencing and RNA sequencing was conducted using the peripheral blood of the twins to find the genes playing important roles in psoriasis pathogenesis.

Results: As a result, we found methylation diversity in four genes (MAST3, MTOR, PM20D1 and ZNF99), and we also found 9 differentially expressed genes (PPAN-P2RY11, PIGV, RPS18, TMEM121, KIF21A, KCNH2, WNT10B, PRX and CDH24) by RNA sequencing. According to the conjoint analysis of methylation and the mRNA results, PTPN6, CCL5, NFATC1 and PRF1 were found to be closely related to psoriasis. We then annotated the genes to explore the associations between these genes and psoriasis.

Conclusions: These findings provide a better understanding of psoriasis that can improve the diagnosis and treatment of the disease.

Keywords: epigenome; monozygotic twins; psoriasis; transcriptome.

MeSH terms

  • Asian People / genetics
  • CD4-Positive T-Lymphocytes*
  • CD8-Positive T-Lymphocytes*
  • Chemokine CCL5 / genetics
  • DNA Methylation
  • Epigenome
  • Female
  • Humans
  • NFATC Transcription Factors / genetics
  • Perforin / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics
  • Psoriasis / blood*
  • Psoriasis / genetics*
  • RNA, Messenger / metabolism
  • Transcriptome
  • Twins, Monozygotic / genetics*

Substances

  • CCL5 protein, human
  • Chemokine CCL5
  • NFATC Transcription Factors
  • NFATC1 protein, human
  • PRF1 protein, human
  • RNA, Messenger
  • Perforin
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6