Development of pulmonary dendritic cells and macrophage subsets

Development of pulmonary DC and macrophage subsets. This model of pulmonary DC and macrophage subset differentiation in mice summarizes recent findings suggesting early lineage commitment of cDCs in the BM and differentiation of monocytes into different population with DC, macrophage, or suppressive functions. All DC subsets present in the lung originate from hematopoietic progenitors (HSC) that differentiate into a common myeloid progenitor (CMP). Such CMPs further differentiate to a common DC progenitors (CDPs) or macrophage DC progenitors (MDPs). MDPs give rise to a common monocyte precursor (cMoP). In a CSF-1-dependent mechanism, Ly6Chi monocytes develop, which can further differentiate into Ly6Clo monocytes. Such Ly6Clo monocytes may also derive directly from cMoPs. Both monocyte populations can enter the lung and become monocyte-derived DCs, macrophages, or suppressor cells (25, 62). CDPs also serve as precursors for pDCs and pre-cDCs. Recent studies suggest that the two cDC populations deriving from the pre-cDC progenitor, i.e., CD103+ cDCs and CD11b+ cDCs, arise already in the bone marrow as pre-cDC1/cDC2 subtypes. One study suggested that pulmonary monocytes may differentiate into pulmonary CD103+ and CD11b+ DC; however, it is unclear whether such cells are phenotypically and functionally identical to CD103+ and CD11b+ cDCs. Activation of defined transcription factors (in blue) at distinct time points is critical for lineage commitment of the different DC precursors. During the early developmental stages, important transcription factors include STAT3, IRF8, and PU.1. At later stages, E2-2 is decisive for pDC commitment of CDPs. BATF3 and IRF8 are associated with the CD103+ cDC and IRF4 with the CD11b+ differentiation. In addition to the transcription factors, several growth factors (in green) play key functions in the development of pre-cDCs and the different DC subsets, in particular Flt3L, CSF-1 (M-CSF), and CSF-2 (GM-CSF). The lung contains two major macrophage populations, i.e., alveolar and interstitial macrophages (AMs and IMs, respectively). It is now well appreciated that AMs derive from yolk sac and fetal liver progenitors that colonize the embryonic lung and are maintained by self-renewal at steady state. The origin of IMs remains elusive. Some data suggest that they represent monocyte-derived macrophages. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3892 CPTAC Assay Portal]

肺泡树突状细胞和巨噬细胞亚群的发育。本研究模型总结了最近的研究成果，指出在骨髓中cDCs的早期谱系决定以及单核细胞分化为具有树突状细胞、巨噬细胞或抑制功能的异质群体。肺中存在的所有树突状细胞亚群均源自造血祖细胞（HSC），这些祖细胞分化为共同髓系祖细胞（CMP）。此类CMP进一步分化为共同树突状细胞祖细胞（CDPs）或巨噬细胞树突状细胞祖细胞（MDPs）。MDPs衍生出共同单核细胞前体（cMoP）。在CSF-1依赖性机制下，Ly6Chi单核细胞发育，这些细胞可以进一步分化为Ly6Clo单核细胞。此类Ly6Clo单核细胞也可能直接源自cMoPs。两种单核细胞群体均可进入肺中并成为单核细胞来源的树突状细胞、巨噬细胞或抑制细胞（25, 62）。CDPs还作为pDCs和前-cDCs的前体。近期研究表明，源自前-cDC祖细胞的两类cDC群体，即CD103+ cDCs和CD11b+ cDCs，已作为前-cDC1/cDC2亚型在骨髓中形成。一项研究提出，肺泡单核细胞可能分化为肺泡CD103+和CD11b+树突状细胞；然而，尚不清楚此类细胞在表型和功能上是否与CD103+和CD11b+ cDCs相同。在特定时间点激活特定的转录因子（以蓝色标注）对于不同树突状细胞祖细胞的谱系决定至关重要。在早期发育阶段，重要的转录因子包括STAT3、IRF8和PU.1。在后期阶段，E2-2对于CDPs的pDC决定至关重要。BATF3和IRF8与CD103+ cDC相关，而IRF4与CD11b+分化相关。除了转录因子外，多种生长因子（以绿色标注）在预-cDCs和不同树突状细胞亚群的发展中发挥关键作用，特别是Flt3L、CSF-1（M-CSF）和CSF-2（GM-CSF）。肺中含有两种主要的巨噬细胞群体，即肺泡巨噬细胞（AMs）和间质巨噬细胞（IMs）。目前普遍认为，AMs源自卵黄囊和胎儿肝脏祖细胞，这些祖细胞定殖于胚胎肺并维持稳态的自我更新。IMs的起源尚不明确。一些数据表明，它们可能是单核细胞来源的巨噬细胞。该通路上的蛋白质具有通过[https://assays.cancer.gov/available_assays?wp_id=WP3892 CPTAC检测门户]可用的靶向检测方法。