气道基底干细胞对于维持功能性上皮内气道巨噬细胞是必需的。
Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages.
作者信息
Kooistra Tristan, Saez Borja, Roche Marly, Egea-Zorrilla Alejandro, Li Dongzhu, Anketell Dilanjan, Nguyen Nhan, Villoria Jorge, Gillis Jacob, Petri Eva, Vera Laura, Blasco-Iturri Zuriñe, Smith Neal P, Alladina Jehan, Zhang Yanting, Vinarsky Vladimir, Shivaraju Manjunatha, Sheng Susan L, Chen Michelle, Gonzalez-Celeiro Meryem, Mou Hongmei, Waghray Avinash, Lin Brian, Paksa Azadeh, Yanger Kilangsungla, Tata Purushotama Rao, Zhao Rui, Causton Benjamin, Zulueta Javier J, Prosper Felipe, Cho Josalyn L, Villani Alexandra-Chloe, Haber Adam, Rajagopal Jayaraj, Medoff Benjamin D, Pardo-Saganta Ana
机构信息
Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Institute for Lung Health (ILH), Department of Internal Medicine, Justus-Liebig University, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), 35392 Giessen, Germany; Cardio-Pulmonary Institute (CPI), Department of Internal Medicine, Justus Liebig University, 35392 Giessen, Germany.
出版信息
Cell Rep. 2025 Jun 24;44(6):115860. doi: 10.1016/j.celrep.2025.115860. Epub 2025 Jun 12.
Stem cells are known to provide signals that contribute to the maintenance and function of neighboring cells. We demonstrate that Notch signaling arising from airway basal stem cells is necessary for the function of a unique population of intraepithelial airway macrophages (IAMs) in the murine trachea. Without this stem cell signaling, IAMs lose MHC II expression, which in turn prevents antigen-induced allergic inflammation. Distal murine airways do not harbor basal stem cells, and, in this region of the lung, allergic inflammation proceeds unperturbed. We speculate that the functional coupling of specific anatomically restricted stem cell populations and adjacent immune cells is one mechanism for ensuring that inflammatory responses are compartmentalized to regions of injury. Basal stem cells are found throughout the human airway tree and we demonstrate the existence of human IAM-like cells, suggesting that their interaction may influence airways disease.
已知干细胞能提供有助于维持邻近细胞及其功能的信号。我们证明，气道基底干细胞产生的Notch信号对于小鼠气管中一类独特的上皮内气道巨噬细胞（IAMs）的功能是必需的。没有这种干细胞信号，IAMs会失去MHC II表达，进而阻止抗原诱导的过敏性炎症。小鼠远端气道没有基底干细胞，在肺的这个区域，过敏性炎症不受干扰地进行。我们推测，特定解剖学限制的干细胞群与相邻免疫细胞的功能耦合是确保炎症反应局限于损伤区域的一种机制。在整个人类气道树中都能发现基底干细胞，并且我们证明了人类中存在类似IAM的细胞，这表明它们之间的相互作用可能会影响气道疾病。
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