Varol Chen, Landsman Limor, Fogg Darin K, Greenshtein Liat, Gildor Boaz, Margalit Raanan, Kalchenko Vyacheslav, Geissmann Frederic, Jung Steffen
Department of Immunology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
J Exp Med. 2007 Jan 22;204(1):171-80. doi: 10.1084/jem.20061011. Epub 2006 Dec 26.
The mononuclear phagocyte (MP) system is a body-wide macrophage (MPhi) and dendritic cell (DC) network, which contributes to tissue homeostasis, inflammation, and immune defense. The in vivo origins of MPs remain poorly understood. Here, we use an adoptive precursor cell transfer strategy into MP-depleted mice to establish the in vivo differentiation sequence from a recently identified MPhi/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood intermediates to peripheral MPhis and DCs. We show that MDPs are in vivo precursors of BM and blood monocytes. Interestingly, grafted Gr1high "inflammatory" blood monocytes shuttle back to the BM in the absence of inflammation, convert into Gr1low monocytes, and contribute further to MP generation. The grafted monocytes give rise to DCs in the intestinal lamina propria and lung, but not to conventional CD11chigh DCs in the spleen, which develop during homeostasis from MDPs without a monocytic intermediate.
单核吞噬细胞（MP）系统是一个遍布全身的巨噬细胞（MPhi）和树突状细胞（DC）网络，它有助于维持组织稳态、炎症反应和免疫防御。MP在体内的起源仍知之甚少。在此，我们采用将前体细胞过继转移到MP耗竭小鼠体内的策略，以建立从最近鉴定出的MPhi/DC限制性骨髓（BM）前体细胞（MDP）通过BM和血液中间细胞到外周MPhi和DC的体内分化序列。我们发现MDP是BM和血液单核细胞的体内前体细胞。有趣的是，移植的Gr1高“炎性”血液单核细胞在无炎症情况下会返回BM，转变为Gr1低单核细胞，并进一步促进MP的生成。移植的单核细胞可在肠道固有层和肺中产生DC，但在脾脏中不会产生传统的CD11c高DC，后者在稳态过程中由MDP产生，无需单核细胞中间阶段。
