Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis.
Differential induction of Ly6G and Ly6C positive myeloid derived suppressor cells in chronic kidney and liver inflammation and fibrosis.
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DOI：
10.1371/journal.pone.0119662
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ludwig-Portugall I
中科院分区：
文献类型：
--
作者：
Höchst B;Mikulec J;Baccega T;Metzger C;Welz M;Peusquens J;Tacke F;Knolle P;Kurts C;Diehl L;Ludwig-Portugall I
已知CD 11b + Gr 1+髓源性抑制细胞（MDSC）是T细胞免疫的非常有效的抑制剂，并且可以在小鼠中分别基于Ly 6 G或Ly 6C的表达进一步分层为粒细胞MDSC和单核细胞MDSC。在这里，使用这些标志物和功能测定，我们的目的是确定MDSC是否在导致肾脏和肝脏纤维化的慢性炎症过程中被诱导，以及其他标志物是否可以更特异地识别这些MDSC亚群。在腺嘌呤诱导的肾脏炎症/纤维化模型中，诱导抑制性Ly 6 Gpos MDSC。Ly 6 G + MDSC群中的抑制功能仅存在于IFNγRβ表达细胞中。相比之下，在胆管结扎诱导的肝脏慢性炎症中，抑制能力仅存在于Ly 6 Cpos MDSC亚群中。基因表达分析证实了这些MDSC亚群的差异起源和调节。此外，肾脏或肝脏纤维化中MDSC的耗竭增强了纤维化标志物，表明MDSC在器官纤维化中具有保护作用。因此，我们的数据表明，在肝脏炎症和肾脏纤维化过程中，具有相似功能的MDSC产生，具有不同的标志物谱，并且来自不同的细胞群。
CD11b+Gr1+ myeloid derived suppressor cells (MDSC) are known to be very potent suppressors of T cell immunity and can be further stratified into granulocytic MDSC and monocytic MDSC in mice based on expression of Ly6G or Ly6C, respectively. Here, using these markers and functional assays, we aimed to identify whether MDSC are induced during chronic inflammation leading to fibrosis in both kidney and liver and whether additional markers could more specifically identify these MDSC subsets. In an adenine-induced model of kidney inflammation/fibrosis suppressive Ly6Gpos MDSC were induced. The suppressive function within the Ly6G+ MDSC population was exclusively present in IFNγRβ expressing cells. In contrast, in chronic inflammation in the liver induced by bile duct ligation, suppressive capacity was exclusively present in the Ly6Cpos MDSC subset. Gene expression analyses confirmed the differential origins and regulation of those MDSC subsets. Additionally, depletion of MDSC in either kidney or liver fibrosis enhanced fibrosis markers, indicating a protective role for MDSC in organ fibrosis. Thus, our data demonstrate that during liver inflammation and kidney fibrosis MDSC with similar function arise bearing a distinct marker profile and arising from different cell populations.
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影响因子：
30.5
作者：
Huang, Li-Rung;Wohlleber, Dirk;Knolle, Percy A.
通讯作者：
Knolle, Percy A.
影响因子：
20.3
作者：
Movahedi, Kiavash;Guilliams, Martin;Van Ginderachter, Jo A.
通讯作者：
Van Ginderachter, Jo A.
影响因子：
11.2
作者：
Sinha, Pratima;Clements, Virginia K.;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
影响因子：
11.2
作者：
Roth, Felix;De La Fuente, Adriana C.;Serafini, Paolo
通讯作者：
Serafini, Paolo
影响因子：
8.6
作者：
Liu, Yu;Zeng, Bin;Yang, Rongcun
通讯作者：
Yang, Rongcun