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Autoimmune and autoinflammatory mechanisms in uveitis

Lee, RW; Nicholson, LB; Sen, HN; Chan, CC; Wei, L; Nussenblatt, RB; Dick, AD; (2014) Autoimmune and autoinflammatory mechanisms in uveitis. Semin Immunopathol , 36 (5) 581 - 594. 10.1007/s00281-014-0433-9. Green open access

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Abstract

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders.

Type: Article
Title: Autoimmune and autoinflammatory mechanisms in uveitis
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00281-014-0433-9
Publisher version: http://dx.doi.org/10.1007/s00281-014-0433-9
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. https://creativecommons.org/licenses/by/3.0/
Keywords: Adaptive Immunity, Animals, Autoimmune Diseases, Autoimmunity, Humans, Molecular Targeted Therapy, Myeloid Cells, Systems Biology, T-Lymphocyte Subsets, Uveitis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1469531
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