Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74⁺ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74⁺ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.

中文翻译：

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感染和炎症刺激 CD74+ 潘氏细胞亚群扩张以调节疾病进展

潘氏细胞（PC）是小肠中的一种特殊分泌细胞类型，人们越来越认识到它在宿主对微生物组和环境压力的反应中发挥着重要作用。共生微生物和病原微生物是否以及如何改变 PC 成分来调节炎症仍不清楚。在常规和限生条件下使用新开发的 PC 报告小鼠，我们在单细胞水平上确定了 PC 转录组异质性对共生和入侵微生物的反应。^{感染扩大了 CD74 +} PC的数量，其数量与小鼠自身或同种异体炎症性疾病的进展相关。在人类炎症疾病组织中也发现了类似的相关性。感染刺激的细胞因子增加活性氧 (ROS) 的产生和活化 PC 中 PC 特异性粘膜五聚蛋白 (Mptx2) 的表达。MyD88的 PC 特异性消融减少了 CD74 ⁺ PC 群体，从而改善了病原体诱导的全身性疾病。在缺乏 Mptx2 的小鼠中也观察到了类似的表型。因此，感染会刺激影响疾病进展的 PC 亚群的扩张。