IL-17A Damages the Blood–Retinal Barrier through Activating the Janus Kinase 1 Pathway

Eimear M. Byrne, María Llorián-Salvador, Miao Tang, Andriana Margariti, Mei Chen, Heping Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Downloads (Pure)

Abstract

Blood–retinal barrier (BRB) dysfunction underlies macular oedema in many sight-threatening conditions, including diabetic macular oedema, neovascular age-related macular degeneration and uveoretinitis. Inflammation plays an important role in BRB dysfunction. This study aimed to understand the role of the inflammatory cytokine IL-17A in BRB dysfunction and the mechanism involved. Human retinal pigment epithelial (RPE) cell line ARPE19 and murine brain endothelial line bEnd.3 were cultured on transwell membranes to model the outer BRB and inner BRB, respectively. IL-17A treatment (3 days in bEnd.3 cells and 6 days in ARPE19 cells) disrupted the distribution of claudin-5 in bEnd.3 cells and ZO-1 in ARPE19 cells, reduced the transepithelial/transendothelial electrical resistance (TEER) and increased permeability to FITC-tracers in vitro. Intravitreal (20 ng/1 μL/eye) or intravenous (20 ng/g) injection of recombinant IL-17A induced retinal albumin leakage within 48 h in C57BL/6J mice. Mechanistically, IL-17A induced Janus kinase 1 (JAK1) phosphorylation in bEnd.3 but not ARPE19 cells. Blocking JAK1 with Tofacitinib prevented IL-17A-mediated claudin-5 dysmorphia in bEnd.3 cells and reduced albumin leakage in IL-17A-treated mice. Our results suggest that IL-17A can damage the BRB through the activating the JAK1 signaling pathway, and targeting this pathway may be a novel approach to treat inflammation-induced macular oedema.
Original languageEnglish
Article number831
JournalBiomedicines
Volume9
Issue number7
Early online date16 Jul 2021
DOIs
Publication statusEarly online date - 16 Jul 2021

Keywords

  • interleukin-17
  • blood–retinal barrier
  • retinopathy
  • macular oedema
  • inflammation
  • retina
  • JAK/STAT signaling
  • Tofacitinib Citrate

Fingerprint

Dive into the research topics of 'IL-17A Damages the Blood–Retinal Barrier through Activating the Janus Kinase 1 Pathway'. Together they form a unique fingerprint.

Cite this