Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York.
Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York; Stony Brook Cancer Center, Stony Brook, New York.
Am J Pathol. 2024 Jun;194(6):927-940. doi: 10.1016/j.ajpath.2024.01.021. Epub 2024 Feb 28.
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity, and mucosal healing is critical for remission. Serine is a nonessential amino acid that supports epithelial and immune cell metabolism and proliferation; however, whether these roles affect IBD pathogenesis is not well understood. Herein, the study showed that serine synthesis increased selectively in the epithelial cells of colons from patients with IBD and murine models of colitis. Inhibiting serine synthesis impaired colonic mucosal healing and increased susceptibility to acute injury in mice, effects associated with diminished epithelial cell proliferation. Dietary removal of serine similarly sensitized mice to acute chemically induced colitis but ameliorated inflammation in chronic colitis models. The anti-inflammatory effect of exogenous serine depletion in chronic colitis was associated with mitochondrial dysfunction of macrophages, resulting in impaired nucleotide production and proliferation. Collectively, these results suggest that serine plays an important role in both epithelial and immune cell biology in the colon and that modulating its availability could impact IBD pathogenesis.
炎症性肠病（IBD）是一种慢性胃肠道炎症性疾病，主要由免疫细胞活动驱动，黏膜愈合对于缓解至关重要。丝氨酸是一种非必需氨基酸，支持上皮细胞和免疫细胞的代谢和增殖；然而，这些作用是否影响 IBD 的发病机制尚不清楚。在此，研究表明，IBD 患者和结肠炎的小鼠模型的结肠上皮细胞中，丝氨酸的合成选择性增加。抑制丝氨酸合成会损害结肠黏膜愈合，并增加小鼠对急性损伤的易感性，这些作用与上皮细胞增殖减少有关。饮食中去除丝氨酸也会使小鼠对急性化学诱导的结肠炎敏感，但可改善慢性结肠炎模型中的炎症。慢性结肠炎中外源丝氨酸耗竭的抗炎作用与巨噬细胞的线粒体功能障碍有关，导致核苷酸生成和增殖受损。总的来说，这些结果表明，丝氨酸在结肠中的上皮细胞和免疫细胞生物学中都起着重要作用，调节其可用性可能会影响 IBD 的发病机制。
