Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway

Pediatr Res. 2019 May;85(6):835-840. doi: 10.1038/s41390-019-0312-0. Epub 2019 Jan 25.

Abstract

Background: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD).

Methods: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively.

Results: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group.

Conclusion: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Child, Preschool
  • Female
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Infant
  • Leukocytes, Mononuclear / immunology
  • Male
  • Mucocutaneous Lymph Node Syndrome / genetics
  • Mucocutaneous Lymph Node Syndrome / immunology*
  • Mucocutaneous Lymph Node Syndrome / therapy
  • NFATC Transcription Factors / blood
  • NFATC Transcription Factors / genetics
  • OX40 Ligand / blood*
  • OX40 Ligand / genetics
  • RNA, Messenger / blood
  • RNA, Messenger / genetics
  • Receptors, OX40 / blood*
  • Receptors, OX40 / genetics
  • Signal Transduction

Substances

  • Immunoglobulins, Intravenous
  • NFATC Transcription Factors
  • NFATC1 protein, human
  • NFATC2 protein, human
  • OX40 Ligand
  • RNA, Messenger
  • Receptors, OX40
  • TNFRSF4 protein, human
  • TNFSF4 protein, human