Autoimmune and autoinflammatory mechanisms in uveitis

Area of Science:

• Ophthalmology
• Immunology
• Systemic Biology

Background:

• The eye possesses unique immunoregulatory mechanisms to maintain tissue function against immune insults.
• Inflammation within the eye, known as uveitis, can result from overt or covert infections.
• Healthy ocular tissues, including the retina, employ myeloid cell regulation, blood-retinal barrier integrity, and immune surveillance for homeostasis.

Purpose of the Study:

• To explore the immunoregulatory mechanisms of the eye and the factors contributing to persistent inflammation in uveitis.
• To investigate the potential role of cryptic infections in driving autoimmune responses in uveitis.
• To compare immune responses in uveitis with those in autoinflammatory disorders.

Main Methods:

• Review of current understanding of ocular immunology and uveitis.
• Extrapolation of findings from animal models to human conditions.
• Application of systems biology approaches and informatics to analyze immune cell phenotypes and functions.

Main Results:

• Disruption of ocular homeostasis leads to inflammation where regulatory mechanisms like T cell apoptosis and Treg generation become less effective.
• Persistent uveitis may involve differential T cell trafficking, CD8(+) T cell residency, and altered myeloid cell function.
• Systems biology suggests shared changes in T cell phenotypes and monocyte function between diseased animals and humans.

Conclusions:

• Ocular immune regulation is complex, involving myeloid cell control, barrier function, and surveillance.
• Failure of anti-inflammatory mechanisms contributes to persistent uveitis.
• A cryptic infectious trigger or altered immune responses, potentially shared with autoinflammatory disorders, may underlie persistent uveitis.