Lechner Andrew J, Driver Ian H, Lee Jinwoo, Conroy Carmen M, Nagle Abigail, Locksley Richard M, Rock Jason R
Department of Anatomy, University of California, San Francisco, CA 94143, USA.
Department of Medicine and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
Cell Stem Cell. 2017 Jul 6;21(1):120-134.e7. doi: 10.1016/j.stem.2017.03.024. Epub 2017 May 11.
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.
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术模型，该模型可促进剩余肺叶中形成新的肺泡。免疫荧光和单细胞RNA测序发现，在2型肺泡上皮干细胞（AEC2）增殖高峰期，CD115 +和CCR2 +单核细胞以及M2样巨噬细胞在肺中积聚。小鼠的基因功能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趋化因子轴迁移至肺，并且与表达Il4ra的白细胞一起，是最佳肺再生所必需的。我们的数据表明，这些细胞调节AEC2的增殖和分化。最后，我们提供证据表明，2型固有淋巴细胞是IL-13的来源，IL-13可促进肺再生。总之，我们的数据突出了免疫调节疗法刺激成人肺泡形成的潜力。
