Karsunky Holger, Merad Miriam, Cozzio Antonio, Weissman Irving L, Manz Markus G
Institute for Research in Biomedicine (IRB), Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
J Exp Med. 2003 Jul 21;198(2):305-13. doi: 10.1084/jem.20030323.
Stimulation of Flt3 receptor tyrosine kinase through its cognate ligand expands early hematopoietic progenitor and dendritic cells (DCs) in humans and mice. The exact developmental stages at which hematopoietic progenitors express Flt3, are responsive to its ligand, and subsequently develop to DCs, are not known. Here we show that common lymphoid and common myeloid progenitors, as well as steady state DCs in thymus, spleen, and epidermis, express Flt3. The receptor is down-regulated once definitive B cell, T cell, and megakaryocyte/erythrocyte commitment occurs, and Flt3 is not detectable on other steady state hematopoietic cell populations. Upon in vivo Flt3 ligand (Flt3L) administration, Flt3+ progenitor cells and their progeny DCs are expanded, whereas Flt3- downstream progenitors are not, or are only slightly increased. Transplantation of common lymphoid and common myeloid progenitors and subsequent Flt3L injection increases progeny DCs of both precursor populations. These findings provide a definitive map of Flt3 expression in the hematopoietic hierarchy and directly demonstrate that Flt3L can drive DC development along both the lymphoid and myeloid developmental pathways from Flt3+ progenitors to Flt3+ DCs.
通过其同源配体刺激Flt3受体酪氨酸激酶可使人类和小鼠的早期造血祖细胞和树突状细胞（DC）扩增。造血祖细胞表达Flt3、对其配体产生反应并随后发育为DC的确切发育阶段尚不清楚。在此我们表明，常见淋巴祖细胞和常见髓系祖细胞，以及胸腺、脾脏和表皮中的稳态DC均表达Flt3。一旦确定B细胞、T细胞和巨核细胞/红细胞定向分化，该受体表达下调，并且在其他稳态造血细胞群体上检测不到Flt3。体内给予Flt3配体（Flt3L）后，Flt3+祖细胞及其子代DC会扩增，而Flt3-下游祖细胞则不会，或仅略有增加。移植常见淋巴祖细胞和常见髓系祖细胞并随后注射Flt3L会增加两个前体细胞群体的子代DC。这些发现提供了造血层级中Flt3表达的确切图谱，并直接证明Flt3L可驱动从Flt3+祖细胞到Flt3+DC的淋巴和髓系发育途径的DC发育。
