Department of Immunology, University of Washington, Seattle, WA 98195, USA.
J Immunol. 2013 Feb 1;190(3):886-91. doi: 10.4049/jimmunol.1202739. Epub 2013 Jan 9.
Mice overexpressing TLR7 (TLR7.1 mice) are a model of systemic lupus erythematosus pathogenesis and exhibit peripheral myeloid expansion. We show that TLR7.1 mice have a dramatic expansion of splenic cells that derive from granulocyte/macrophage progenitors (GMP) compared with wild-type mice. In the bone marrow, TLR7.1 mice exhibited hallmarks of emergency myelopoiesis and contained a discrete population of Sca-1(+) GMP, termed emergency GMP, which are more proliferative and superior myeloid precursors than classical Sca-1(-) GMP. The emergency myelopoiesis and peripheral myeloid expansion in TLR7.1 mice was dependent on type I IFN signaling. TLR7 agonist administration to nontransgenic mice also drove type I IFN-dependent emergency myelopoiesis. TLR7.1 plasmacytoid dendritic cells were cell-intrinsically activated by TLR7 overexpression and constitutively produced type I IFN mRNA. This study shows that type I IFN can act upon myeloid progenitors to promote the development of emergency GMP, which leads to an expansion of their progeny in the periphery.
过度表达 TLR7（TLR7.1 小鼠）的小鼠是全身性红斑狼疮发病机制的模型，表现出外周髓系细胞扩增。我们发现与野生型小鼠相比，TLR7.1 小鼠的脾脏细胞来自粒细胞/巨噬细胞前体（GMP）的明显扩增。在骨髓中，TLR7.1 小鼠表现出应急髓样细胞生成的特征，并包含离散的 Sca-1(+)GMP 群体，称为应急 GMP，其增殖能力更强，是比经典 Sca-1(-)GMP 更优秀的髓样前体。TLR7.1 小鼠中的应急髓样细胞生成和外周髓系细胞扩增依赖于 I 型 IFN 信号。TLR7 激动剂给药给非转基因小鼠也会导致 I 型 IFN 依赖性应急髓样细胞生成。TLR7.1 浆细胞样树突状细胞通过 TLR7 过表达而内在激活，并持续产生 I 型 IFN mRNA。本研究表明，I 型 IFN 可以作用于髓样前体以促进应急 GMP 的发育，从而导致其在外周的后代扩增。
