TIM-3 regulates innate immune cells to induce fetomaternal tolerance.
TIM-3 regulates innate immune cells to induce fetomaternal tolerance.
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DOI：
10.4049/jimmunol.1202176
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Guleria I
中科院分区：
文献类型：
--
作者：
Chabtini L;Mfarrej B;Mounayar M;Zhu B;Batal I;Dakle PJ;Smith BD;Boenisch O;Najafian N;Akiba H;Yagita H;Guleria I
TIM-3在巨噬细胞和树突状细胞的亚群上组成性表达。其在先天免疫系统的其他细胞上的表达及其在母胎耐受中的作用尚未被探索。在这里，我们调查的作用TIM-3表达先天免疫细胞在调节耐受性的母胎界面（FMI）使用同种异体小鼠妊娠模型。TIM-3的阻断导致炎性粒细胞和巨噬细胞在子宫-胎盘界面处的积累以及促炎细胞因子的上调。此外，TIM-3阻断剂抑制子宫巨噬细胞的吞噬潜能，导致凋亡小体在子宫-胎盘界面处积聚，引起局部免疫应答。响应于炎性细胞因子，诱导表达iNOS和iNOS酶1的Ly-6ChiGneg M-MDSC（单核细胞髓源性抑制细胞）。然而，这些抑制性细胞不能下调由炎性粒细胞（Ly-6Cint Ghi）和凋亡细胞诱导的炎症级联反应;炎性粒细胞产生的IFNγ和TNFα增加导致母胎界面耐受性的消除和胎儿排斥。这些数据突出了FMI处先天免疫系统细胞之间的相互作用及其对小鼠成功妊娠的影响。
TIM-3 is constitutively expressed on subsets of macrophages and dendritic cells. Its expression on other cells of the innate immune system and its role in fetomaternal tolerance has not yet been explored. Here we investigate the role of TIM-3 expressing innate immune cells in the regulation of tolerance at the fetomaternal interface (FMI) using an allogeneic mouse model of pregnancy. Blockade of TIM-3 results in accumulation of inflammatory granulocytes and macrophages at the utero-placental interface and up regulation of pro-inflammatory cytokines. Furthermore, TIM-3 blockade inhibits the phagocytic potential of uterine macrophages resulting in a build up of apoptotic bodies at the utero-placental interface that elicits a local immune response. In response to inflammatory cytokines, Ly-6ChiGneg M-MDSCs (monocytic myeloid derived suppressor cells) expressing iNOS and arginase 1 are induced. However, these suppressive cells fail to down-regulate the inflammatory cascade induced by inflammatory granulocytes (Ly-6Cint Ghi) and apoptotic cells; the increased production of IFNγ and TNFα by inflammatory granulocytes leads to abrogation of tolerance at the fetomaternal interface and fetal rejection. These data highlight the interplay between cells of the innate immune system at the FMI and their influence on successful pregnancy in mice.
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DOI：
10.4049/jimmunol.0903435
发表时间：
2010-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boenisch O;D'Addio F;Watanabe T;Elyaman W;Magee CN;Yeung MY;Padera RF;Rodig SJ;Murayama T;Tanaka K;Yuan X;Ueno T;Jurisch A;Mfarrej B;Akiba H;Yagita H;Najafian N
通讯作者：
Najafian N
影响因子：
82.9
作者：
Blois, Sandra M.;Ilarregui, Juan M.;Arck, Petra C.
通讯作者：
Arck, Petra C.
影响因子：
6
作者：
Crocker, IP;Cooper, S;Baker, PN
通讯作者：
Baker, PN
DOI：
10.1084/jem.20082429
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hafler DA;Kuchroo V
通讯作者：
Kuchroo V
影响因子：
4.4
作者：
Kashio, Y;Nakamura, K;Hirashima, M
通讯作者：
Hirashima, M