Whole transcriptome analysis of myeloid dendritic cells reveals distinct genetic regulation in patients with allergies

Kijeong Lee, Mi Ryung Han, Ji Woo Yeon, Byoungjae Kim, Tae Hoon Kim

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Dendritic cells (DCs) play critical roles in atopic diseases, orchestrating both innate and adaptive immune systems. Nevertheless, limited information is available regarding the mechanism through which DCs induce hyperresponsiveness in patients with allergies. This study aims to reveal novel genetic alterations and future therapeutic target molecules in the DCs from patients with allergies using whole transcriptome sequencing. Transcriptome sequencing of human BDCA-3+/CD11c+ DCs sorted from peripheral blood monocytes obtained from six patients with allergies and four healthy controls was conducted. Gene expression profile data were analyzed, and an ingenuity pathway analysis was performed. A total of 1638 differentially expressed genes were identified at p-values < 0.05, with 11 genes showing a log2-fold change ≥1.5. The top gene network was associated with cell death/survival and organismal injury/abnormality. In validation experiments, amphiregulin (AREG) showed consistent results with transcriptome sequencing data, with increased mRNA expression in THP-1-derived DCs after Der p 1 stimulation and higher protein expression in myeloid DCs obtained from patients with allergies. This study suggests an alteration in the expression of DCs in patients with allergies, proposing related altered functions and intracellular mechanisms. Notably, AREG might play a crucial role in DCs by inducing the Th2 immune response.

Original languageEnglish
Article number8640
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume21
Issue number22
DOIs
Publication statusPublished - 2020 Nov 2

Bibliographical note

Funding Information:
Funding: This research was supported by the Basic Science Research Program, National Research Foundation of Korea, funded by the Ministry of Science and Technology and the Ministry of Science, ICT & Future Planning (2017R1A2B2003575, NRF-2020R1A2C1006398), the Ministry of Science and ICT (2020R1C1C1012288), Korea, under the ICT Creative Consilience program(IITP-2020-0018190011001) supervised by the IITP (Institute for Information & Communications Technology Planning & Evaluation, and the Korea Health Technology R&D Project (HI17C0387), Korea Health Industry Development Institute (KHIDI), and the Ministry of Health & Welfare. This research was also supported by a Korea University grant and a grant from Korea University Medical Center and Anam Hospital, Seoul, Korea.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Allergic rhinitis
  • Allergy
  • Amphiregulin
  • Dendritic cells
  • Gene networks
  • RNA sequencing
  • Transcriptome sequencing

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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