美国斯坦福大学Irving L. Weissman等研究人员合作发现，去除髓系造血干细胞可使衰老的免疫力恢复活力。相关论文于2024年3月27日在线发表于国际学术期刊《自然》。

研究人员表示，免疫系统衰老的特点是淋巴造血和适应性免疫功能下降，炎症和骨髓病变增加。与年龄相关的自我更新造血干细胞（HSC）群体的变化被认为是这些现象的根源。年轻时，淋巴细胞和髓样细胞均衡输出的造血干细胞（bal-HSC）比髓样细胞偏向输出的造血干细胞（my-HSC）占优势，从而促进了启动适应性免疫反应所需的淋巴细胞生成，同时限制了髓样细胞的生成，而髓样细胞可能具有促炎作用。

衰老与my-HSC比例增加有关，导致淋巴细胞生成减少和骨髓细胞生成增加。转移bal-HSC会产生大量淋巴细胞和骨髓细胞，这种稳定的表型在二次转移后仍会保留；而bal-HSC在二次转移后也会保留其生成模式。这两个亚群的起源和潜在的相互转化仍不清楚。如果它们在出生后是独立的亚群，那么就有可能通过消除老龄小鼠的my-HSC来逆转衰老表型。

研究人员证明了抗体介导的老年小鼠my-HSC耗竭可恢复更年轻免疫系统的特征，包括增加普通淋巴细胞祖细胞、初始T细胞和B细胞，同时降低与年龄相关的免疫衰退标志物。在老年小鼠体内去除my-HSC可改善对病毒感染的初级和次级适应性免疫反应。这些发现可能有助于了解和干预因my-HSC主导造血系统而加重或引起的疾病。

附：英文原文

Title: Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity

Author: Ross, Jason B., Myers, Lara M., Noh, Joseph J., Collins, Madison M., Carmody, Aaron B., Messer, Ronald J., Dhuey, Erica, Hasenkrug, Kim J., Weissman, Irving L.

Issue&Volume: 2024-03-27

Abstract: Ageing of the immune system is characterized by decreased lymphopoiesis and adaptive immunity, and increased inflammation and myeloid pathologies1,2. Age-related changes in populations of self-renewing haematopoietic stem cells (HSCs) are thought to underlie these phenomena3. During youth, HSCs with balanced output of lymphoid and myeloid cells (bal-HSCs) predominate over HSCs with myeloid-biased output (my-HSCs), thereby promoting the lymphopoiesis required for initiating adaptive immune responses, while limiting the production of myeloid cells, which can be pro-inflammatory4. Ageing is associated with increased proportions of my-HSCs, resulting in decreased lymphopoiesis and increased myelopoiesis3,5,6. Transfer of bal-HSCs results in abundant lymphoid and myeloid cells, a stable phenotype that is retained after secondary transfer; my-HSCs also retain their patterns of production after secondary transfer5. The origin and potential interconversion of these two subsets is still unclear. If they are separate subsets postnatally, it might be possible to reverse the ageing phenotype by eliminating my-HSCs in aged mice. Here we demonstrate that antibody-mediated depletion of my-HSCs in aged mice restores characteristic features of a more youthful immune system, including increasing common lymphocyte progenitors, naive T cells and B cells, while decreasing age-related markers of immune decline. Depletion of my-HSCs in aged mice improves primary and secondary adaptive immune responses to viral infection. These findings may have relevance to the understanding and intervention of diseases exacerbated or caused by dominance of the haematopoietic system by my-HSCs.

DOI: 10.1038/s41586-024-07238-x

Source: https://www.nature.com/articles/s41586-024-07238-x