角膜缘干细胞（LSC）缺陷是化学性眼部损伤后经常出现的严重并发症。先前的研究假定这是由腐蚀剂直接介导的。本研究表明，即使没有直接损伤LSCs，LSC损伤也是由免疫细胞介导的。特别是，前房（AC）内pH值升高引起的虹膜急性应激，导致基底角膜组织中炎症细胞因子的释放以及随后的LSC损伤和死亡。周围型C-C趋化因子受体2阳性/CX3C趋化因子受体1阴性（CCR2+ CX3CR1-）单核细胞是通过上调肿瘤坏死因子-α（TNF-α）在角膜缘处介导LSC损伤的关键因素。相比外周来源的单核细胞，CX3CR1+ CCR2-组织内驻留巨噬细胞具有保护作用，其在损伤前的消耗加重了LSC损失并增加了LSC对TNF-α介导的凋亡的敏感性，而这与CCR2+细胞浸润组织的无关。一致的是，组织内新出现的巨噬细胞不仅恢复了巨噬细胞的保护性M2样表型，还抑制了暴露于炎性信号后的LSC损失。这些发现可能在化学烧伤或其他炎症情况下导致LSC损失的患者中具有临床意义。

Limbal stem cell (LSC) deficiency is a frequent and severe complication after chemical injury to the eye. Previous studies have assumed this is mediated directly by the caustic agent. Here we show that LSC damage occurs through immune cell mediators, even without direct injury to LSCs. In particular, pH elevation in the anterior chamber (AC) causes acute uveal stress, the release of inflammatory cytokines at the basal limbal tissue, and subsequent LSC damage and death. Peripheral C-C chemokine receptor type 2 positive/CX3C motif chemokine receptor 1 negative (CCR2+ CX3CR1-) monocytes are the key mediators of LSC damage through the upregulation of tumor necrosis factor-alpha (TNF-α) at the limbus. In contrast to peripherally derived monocytes, CX3CR1+ CCR2- tissue-resident macrophages have a protective role, and their depletion prior to injury exacerbates LSC loss and increases LSC vulnerability to TNF-α-mediated apoptosis independently of CCR2+ cell infiltration into the tissue. Consistently, repopulation of the tissue by new resident macrophages not only restores the protective M2-like phenotype of macrophages but also suppresses LSC loss after exposure to inflammatory signals. These findings may have clinical implications in patients with LSC loss after chemical burns or due to other inflammatory conditions.