Dendritic cell physiology and function in the eye

John Vincent Forrester, Heping Xu, Lucia Kuffova, Andrew D. Dick, Paul G. McMenamin

Research output: Contribution to journalLiterature review

105 Citations (Scopus)

Abstract

The eye and the brain are immunologically privileged sites, a property previously attributed to the lack of a lymphatic circulation. However, recent tracking studies confirm that these organs have good communication through classical site-specific lymph nodes, as well as direct connection through the blood circulation with the spleen. In addition, like all tissues, they contain resident myeloid cell populations that play important roles in tissue homeostasis and the response to foreign antigens. Most of the macrophage and dendritic cell (DC) populations in the eye are restricted to the supporting connective tissues, including the cornea, while the neural tissue (the retina) contains almost no DCs, occasional macrophages (perivascularly distributed), and a specialized myeloid cell type, the microglial cell. Resident microglial cells are normally programmed for immunological tolerance. The privileged status of the eye, however, is relative, as it is susceptible to immune-mediated inflammatory disease, both infectious and autoimmune. Intraocular inflammation (uveitis and uveoretinitis) and corneal graft rejection constitute two of the more common inflammatory conditions affecting the eye leading to considerable morbidity (blindness). As corneal graft rejection occurs almost exclusively by indirect allorecognition, host DCs play a major role in this process and are likely to be modified in their behavior by the ocular microenvironment. Ocular surface disease, including allergy and atopy, also comprise a significant group of immune-mediated eye disorders in which DCs participate, while infectious disease such as herpes simplex keratitis is thought to be initiated via corneal DCs. Intriguingly, some more common conditions previously thought to be degenerative (e.g. age-related macular degeneration) may have an autoimmune component in which ocular DCs and macrophages are critically involved. Recently, the possibility of harnessing the tolerizing potential of DCs has been applied to experimental models of autoimmune uveoretinitis with good effect. This approach has considerable potential for use in translational clinical therapy to prevent sight-threatening disease caused by ocular inflammation.

Original languageEnglish
Pages (from-to)282-304
Number of pages23
JournalImmunological Reviews
Volume234
Issue number1
Early online date22 Feb 2010
DOIs
Publication statusPublished - Mar 2010

Keywords

  • dendritic cells
  • tolerance
  • autoimmunity
  • cell trafficking
  • in vivo imaging
  • transplantation
  • regulatoryT-cells
  • experimental autoimmune uveoretinitis
  • resident-tissue macrophages
  • corneal epithelial-cells
  • antigen-presenting cells
  • MHC class-II
  • experimental allergic uveitis
  • draining lymph-nodes
  • toll-like receptors
  • in-vivo

Cite this

Forrester, J. V., Xu, H., Kuffova, L., Dick, A. D., & McMenamin, P. G. (2010). Dendritic cell physiology and function in the eye. Immunological Reviews, 234(1), 282-304. https://doi.org/10.1111/j.0105-2896.2009.00873.x