To investigate the role of immune cells in lung regeneration, we used a unilateral pneumonectomy model that promotes the formation of new alveoli in the remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+ and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss of function in mice and adoptive transfer studies revealed that bone marrow-derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine axis and are required for optimal lung regeneration, along with Il4ra-expressing leukocytes. Our data suggest that these cells modulate AEC2 proliferation and differentiation. Finally, we provide evidence that group 2 innate lymphoid cells are a source of IL-13, which promotes lung regeneration. Together, our data highlight the potential for immunomodulatory therapies to stimulate alveologenesis in adults.

中文翻译：

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肺切除术后招募的单核细胞和2型免疫促进肺再生

为了研究免疫细胞在肺再生中的作用，我们使用了单侧肺切除模型，该模型可促进其余肺叶中新肺泡的形成。免疫荧光法和单细胞RNA测序发现，在2型肺泡上皮干细胞（AEC2）增殖高峰期间，CD115 +和CCR2 +单核细胞以及M2样巨噬细胞在肺中积聚。小鼠功能的遗传丧失和过继转移研究表明，骨髓来源的巨噬细胞（BMDM）通过CCL2-CCR2趋化因子轴运输至肺部，是最佳肺再生以及表达Il4ra的白细胞所必需的。我们的数据表明这些细胞调节AEC2增殖和分化。最后，我们提供证据表明第2组先天性淋巴样细胞是IL-13的来源，IL-13可促进肺再生。一起，