Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
Lab Invest. 2021 Mar;101(3):274-279. doi: 10.1038/s41374-020-00520-2. Epub 2020 Dec 9.
Disorders involving injury to tissue stem cells that ensure normal tissue homeostasis and repair have potential to show unusually devastating clinical consequences. Acute graft-versus-host disease (aGVHD) is one condition where relatively few cytotoxic immune cells target skin stem cells to produce significant morbidity and mortality. By analogy, SARS-CoV-2 is a vector that initially homes to pulmonary stem cells that preferentially express the ACE2 receptor, thus potentially incurring similarly robust pathological consequences. In older individuals, stem cell number and/or function become depleted due to pathways independent of disease-related injury to these subpopulations. Accordingly, pathologic targeting of stem cells in conditions like aGVHD and COVID-19 infection where these cells are already deficient due to the aging process may have dire consequences in elderly individuals. A hypothesis is herein advanced that, as with aGVHD, lung stem cell targeting is a potential co-factor in explaining age-related severity of COVID-19 infection.
涉及组织干细胞损伤的疾病可确保正常组织内稳态和修复，但有可能表现出异常严重的临床后果。急性移植物抗宿主病 (aGVHD) 是一种情况，相对较少的细胞毒性免疫细胞靶向皮肤干细胞，从而产生显著的发病率和死亡率。类似地，SARS-CoV-2 是一种载体，最初定位于优先表达 ACE2 受体的肺干细胞，从而可能产生类似的强大病理后果。在老年人中，由于与疾病相关的损伤无关的途径，干细胞数量和/或功能会耗尽。因此，在像 aGVHD 和 COVID-19 感染这样的情况下，这些细胞由于衰老过程已经不足，对干细胞的病理性靶向治疗可能会对老年人产生可怕的后果。本文提出了一个假设，即与 aGVHD 一样，肺干细胞靶向治疗可能是解释 COVID-19 感染与年龄相关严重程度的一个潜在共同因素。
