Stem cells are known for their resilience and enhanced activity post-stress. The mammary gland undergoes frequent remodeling and is subjected to recurring stress during the estrus cycle, but it remains unclear how mammary stem cells (MaSCs) respond to the stress and contribute to regeneration. We discovered that cytotoxic stress-induced activation of CD11c ductal macrophages aids stem cell survival and prevents differentiation. These macrophages boost Procr MaSC activity through IL1β-IL1R1-NF-κB signaling during the estrus cycle in an oscillating manner. Deleting IL1R1 in MaSCs results in stem cell loss and skewed luminal differentiation. Moreover, under cytotoxic stress from the chemotherapy agent paclitaxel, ductal macrophages secrete higher IL1β levels, promoting MaSC survival and preventing differentiation. Inhibiting IL1R1 sensitizes MaSCs to paclitaxel. Our findings reveal a recurring inflammatory process that regulates regeneration, providing insights into stress-induced inflammation and its impact on stem cell survival, potentially affecting cancer therapy efficacy.

中文翻译：

---

生态位炎症信号控制振荡乳腺再生并保护干细胞免受细胞毒性应激

干细胞以其恢复能力和增强的应激后活性而闻名。乳腺经历频繁的重塑，并在发情周期中承受反复的压力，但目前尚不清楚乳腺干细胞 (MaSC) 如何应对压力并促进再生。我们发现细胞毒性应激诱导的 CD11c 导管巨噬细胞激活有助于干细胞存活并阻止分化。这些巨噬细胞在发情周期期间通过 IL1β-IL1R1-NF-κB 信号以振荡方式增强 Procr MaSC 活性。删除 MaSC 中的 IL1R1 会导致干细胞损失和管腔分化倾斜。此外，在化疗药物紫杉醇的细胞毒性应激下，导管巨噬细胞会分泌更高水平的 IL1β，促进 MaSC 存活并阻止分化。抑制 IL1R1 可使 MaSC 对紫杉醇敏感。我们的研究结果揭示了调节再生的反复炎症过程，提供了对压力诱导的炎症及其对干细胞存活的影响的见解，可能会影响癌症治疗的效果。