Induction of M2-like macrophages in recipient NOD-scid mice by allogeneic donor CD4+CD25+ regulatory T cells
Induction of M2-like macrophages in recipient NOD-scid mice by allogeneic donor CD4+CD25+ regulatory T cells
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DOI：
10.1038/cmi.2012.47
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发表时间：
2012-11-01
影响因子：
24.1
通讯作者：
Zhao, Yong
中科院分区：
文献类型：
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作者：
Hu, Xuelian;Liu, Guangwei;Zhao, Yong
CD4(+)CD25（+）调节性T细胞（Tregs）通过调节先天免疫细胞和适应性免疫细胞的表型和功能，在维持宿主免疫耐受中发挥重要作用。同种异体CD4(+)CD25(+) Tregs是否能调节受体小鼠巨噬细胞尚不清楚。采用小鼠模型，将同种异体供体CD4(+)CD25(+) Tregs过继转移到宿主NOD-scid小鼠腹腔，研究同种异体供体CD4(+)CD25(+) Tregs对受体小鼠F4/80（+）巨噬细胞的影响。然后检测受体巨噬细胞的表型和功能。与接受同种异体CD4(+)CD25(+) Tregs的小鼠相比，接受同种异体CD4(+)CD25(+) Tregs的小鼠腹膜F4/80（+）巨噬细胞表达的CD23和程序性细胞死亡配体1（PD-L1）水平显著升高，CD80、CD86、CD40和MHC II分子水平显著降低。注射同种异体供体CD4(+)CD25(+) Tregs后，受体小鼠的F4/80（+）巨噬细胞对鸡红细胞（cRBCs）的吞噬能力和精氨酸酶活性显著增加，IL-10的产生增加，而这些巨噬细胞的免疫原性和一氧化氮（NO）的产生也下降。阻断精氨酸酶部分但显著地逆转了CD4(+)CD25(+) Tregs在体内诱导M2巨噬细胞的作用。因此，同种异体供体CD4(+)CD25(+) Tregs至少部分通过精氨酸酶途径诱导受体小鼠M2巨噬细胞。我们已经提供了体内证据来支持同种异体供体CD4(+)CD25(+) Tregs通过促进M2巨噬细胞分化来调节受体小鼠先天免疫的未知途径。细胞与分子免疫学（2012）9,464-472；doi: 10.1038 / cmi.2012.47;2012年10月22日在线发布
CD4(+)CD25(+) regulatory T cells (Tregs) play an important role in maintaining host immune tolerance via regulation of the phenotype and function of the innate and adaptive immune cells. Whether allogeneic CD4(+)CD25(+) Tregs can regulate recipient mouse macrophages is unknown. The effect of allogeneic donor CD4(+)CD25(+) Tregs on recipient mouse resident F4/80(+) macrophages was investigated using a mouse model in which allogeneic donor CD4(+)CD25(+) Tregs were adoptively transferred into the peritoneal cavity of host NOD-scid mice. The phenotype and function of the recipient macrophages were then assayed. The peritoneal F4/80(+) macrophages in the recipient mice that received the allogeneic CD4(+)CD25(+) Tregs expressed significantly higher levels of CD23 and programmed cell death-ligand 1(PD-L1) and lower levels of CD80, CD86, CD40 and MHC II molecules compared to the mice that received either allogeneic CD4(+)CD25(-) T cells (Teffs) or no cells. The resident F4/80(+) macrophages of the recipient mice injected with the allogeneic donor CD4(+)CD25(+) Tregs displayed significantly increased phagocytosis of chicken red blood cells (cRBCs) and arginase activity together with increased IL-10 production, whereas these macrophages also showed decreased immunogenicity and nitric oxide (NO) production. Blocking arginase partially but significantly reversed the effects of CD4(+)CD25(+) Tregs with regard to the induction of the M2 macrophages in vivo. Therefore, the allogeneic donor CD4(+)CD25(+) Tregs can induce the M2 macrophages in recipient mice at least in part via an arginase pathway. We have provided in vivo evidence to support the unknown pathways by which allogeneic donor CD4(+)CD25(+) Tregs regulate innate immunity in recipient mice by promoting the differentiation of M2 macrophages. Cellular & Molecular Immunology (2012) 9, 464-472; doi:10.1038/cmi.2012.47; published online 22 October 2012