Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9

Research output: Contribution to journalArticle


Type 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.


  • Neil S. Lagali
  • Reza A. Badian
  • Xu Liu
  • Tobias R. Feldreich
  • Johan Ärnlöv
  • Tor Paaske Utheim
  • Lars B. Dahlin
  • Olov Rolandsson
External organisations
  • Linköping University
  • Oslo university hospital
  • Uppsala University
  • Dalarna University
  • Karolinska Institutet
  • Umeå University
  • Sørlandet Hospital
  • University of Oslo
  • University of South-Eastern Norway
  • Øyelegesenteret AS
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Ophthalmology
Original languageEnglish
Article number14248
JournalScientific Reports
Issue number1
Publication statusPublished - 2018
Publication categoryResearch