Retinal microglia exacerbate uveitis by functioning as local antigen-presenting cells.

Area of Science:

• Ophthalmology
• Immunology
• Neuroscience

Background:

• Autoimmune uveitis (EAU) is a leading cause of blindness.
• EAU pathogenesis involves T cells and retinal antigen-presenting cells (APCs).
• The roles of microglia and dendritic cells (DCs) as APCs in EAU are unclear.

Approach:

• Used genetically modified mice lacking MHC class II on microglia or CD11c+ DCs.
• Induced EAU via conventional and adoptive transfer methods.
• Analyzed APC function across EAU phases.

Key Points:

• Microglia are essential APCs throughout all EAU phases.
• Infiltrating CD11c+ DCs present antigen but are not required for all EAU phases.
• MHC class II expression on microglia is crucial for EAU development.

Conclusions:

• Retinal microglia are the critical APCs in EAU.
• Targeting microglia offers a potential therapeutic strategy for preventing/reducing uveitis.
• Dendritic cell function is less critical than microglia in this model.