Autoimmune and autoinflammatory mechanisms in uveitis

作者：Richard Lee, Lindsay B. Nicholson, Hatice Nida Sen, Chi‐Chao Chan, Lai Wei, Robert Burton Nussenblatt, Andrew D. Dick · 发表于：Seminars in Immunopathology · 年份：2014 · DOI：10.1007/s00281-014-0433-9 · 被引用次数：190 · 研究领域：Ocular Diseases and Behçet’s Syndrome、Cytomegalovirus and herpesvirus research、interferon and immune responses

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 poss...