Ifi27l2a Facilitates the Recruitment of Pathogenic T Cells by Retinal Microglia in the Initiation Phase of Experimental Autoimmune Uveoretinitis

The mechanisms by which pathogenic T cells enter the immune‐privileged retina at the onset of uveitis remain unclear. To identify regulatory targets that promote retinal inflammation, we established an experimental autoimmune uveoretinitis (EAU) model by immunizing C57BL/6J mice with IRBP 651–670 and dynamically evaluated retinal inflammation after induction; fundus lesions were prominent, with the first 14 days representing the initiation phase, Days 14–28 the amplification phase, Days 28–35 the peak phase, and Days 35–42 the regression phase. We characterized retinal cellular alterations from the pre‐inflammatory stage to the peak stage using single‐cell transcriptomic analysis, and found that retinal immune cells changed in parallel with EAU severity, while immune‐cell interactions were strongest on Day 14, especially between microglia and T cells through multiple chemokine‐related pathways. We then identified key cell populations and candidate targets through integrated analyses and functional validation, and Ifi27l2a emerged as a core gene associated with inflammatory and immune responses in retinal microglia on Day 14. In vitro knockdown of Ifi27l2a in LPS‐activated BV‐2 cells reduced inflammatory mediator production and abolished Th1/Th17 induction. In vivo targeting of Ifi27l2a attenuated EAU severity and restored the balance of T‐cell subsets. These findings indicate that microglia are highly activated before retinal inflammation becomes prominent and that Ifi27l2a regulates this early pathogenic process.