Characterizing the distributions of IDO-1 expressing macrophages/microglia in human and murine brains and evaluating the immunological and physiological roles of IDO-1 in RAW264.7/BV-2 cells.
Characterizing the distributions of IDO-1 expressing macrophages/microglia in human and murine brains and evaluating the immunological and physiological roles of IDO-1 in RAW264.7/BV-2 cells.
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DOI：
10.1371/journal.pone.0258204
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Ji R;Ma L;Chen X;Sun R;Zhang L;Saiyin H;Wei W
吲哚胺2，3-双加氧酶1（IDO-1）是一种在胎盘、肿瘤细胞和巨噬细胞中表达的免疫抑制酶，通过将色氨酸转化为犬尿氨酸来排斥T细胞。然而，IDO-1在脑免疫中的作用，特别是在脑膜中的作用尚不清楚。我们的目的是阐明IDO-1+巨噬细胞/小胶质细胞在人脑组织、人胶质母细胞瘤、APP/PS1小鼠脑和喹啉酸模型脑中的分布模式，并探索IDO-1+巨噬细胞/小胶质细胞的生理和免疫作用。在这里，我们发现人和小鼠血管周围和蛛网膜下腔的巨噬细胞/小胶质细胞以及胶质母细胞瘤（GBM）表达IDO-1，但实质的巨噬细胞/小胶质细胞不表达IDO-1。使用包括1-MT和INCB 24360的IDO-1抑制剂，我们观察到抑制IDO-1降低了人血单核细胞和RAW264.7/BV-2细胞的细胞大小和丝状伪足生长、液体摄取以及巨噬细胞和吞噬能力。用1-MT或INCB 24360抑制IDO-1可增加RAW 264.7/BV-2细胞中IL-1β的分泌并抑制NLRP 3的表达。我们的数据共同表明，IDO-1在血管周围和脑膜巨噬细胞/小胶质细胞中的表达增加了细胞吞噬能力，并可能抑制炎症反应的过度活化。
Indoleamine 2,3-dioxygenase 1 (IDO-1) is an immunosuppressive enzyme expressed in the placenta, neoplastic cells, and macrophages to reject T cells by converting tryptophan into kynurenine. However, the role of IDO-1 in brain immunity, especially in the meninges, is unclear. We aim to elucidate the distribution pattern of IDO-1+ macrophages/microglia in the human brain tissues, human glioblastoma, APP/PS1 mouse brains, and quinolinic acid model brains and explore the physiological and immunological roles of IDO-1+ macrophages/microglia. Here, we find that both human and mouse macrophages/microglia of the perivascular and subarachnoid space and in glioblastoma (GBM) expressed IDO-1 but not macrophages/microglia of parenchyma. Using IDO-1 inhibitors including 1-MT and INCB24360, we observed that inhibiting IDO-1 reduced the cellular size and filopodia growth, fluid uptake, and the macropinocytic and phagocytic abilities of human blood monocytes and RAW264.7/BV-2 cells. Inhibiting IDO-1 with 1-MT or INCB24360 increased IL-1β secretion and suppressed NLRP3 expression in RAW264.7/BV-2 cells. Our data collectively show that IDO-1 expression in perivascular and meninges macrophages/microglia increases cellular phagocytic capacity and might suppress overactivation of inflammatory reaction.
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影响因子：
15.9
作者：
Blair, Alex B.;Kleponis, Jennifer;Zheng, Lei
通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1093/brain/aww270
发表时间：
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期刊：
Brain : a journal of neurology
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DOI：
10.1126/science.abf9277
发表时间：
2021-07-23
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Brioschi S;Wang WL;Peng V;Wang M;Shchukina I;Greenberg ZJ;Bando JK;Jaeger N;Czepielewski RS;Swain A;Mogilenko DA;Beatty WL;Bayguinov P;Fitzpatrick JAJ;Schuettpelz LG;Fronick CC;Smirnov I;Kipnis J;Shapiro VS;Wu GF;Gilfillan S;Cella M;Artyomov MN;Kleinstein SH;Colonna M
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影响因子：
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作者：
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通讯作者：
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