Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice.
Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice.
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DOI：
10.1038/s41467-021-25590-8
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发表时间：
2021-09-06
影响因子：
16.6
通讯作者：
Eyo UB
中科院分区：
文献类型：
--
作者：
Bisht K;Okojie KA;Sharma K;Lentferink DH;Sun YY;Chen HR;Uweru JO;Amancherla S;Calcuttawala Z;Campos-Salazar AB;Corliss B;Jabbour L;Benderoth J;Friestad B;Mills WA 3rd;Isakson BE;Tremblay MÈ;Kuan CY;Eyo UB
小胶质细胞是一种在大脑中具有多种功能的免疫细胞。然而，它们与脉管系统的相互作用程度以及对血管生理的潜在调节尚未得到充分的探讨。在这里，我们记录了分支CX3CR1 +髓样细胞躯体和脑毛细血管之间的相互作用。我们通过分子、形态学和超微结构的方法证实这些细胞是真正的小胶质细胞。然后，我们给出了这些毛细血管相关小胶质细胞（CAMs）的详细时空特征，并将它们与实质小胶质细胞（PCMs）在小胶质细胞耗竭和再生过程中的形态活动进行了比较。在分子上，我们发现P2RY12受体在pannexin 1 （PANX1）通道释放嘌呤的控制下作为CAM相互作用的调节因子。此外，在P2RY12 - / -和PANX1 - / -小鼠中，小胶质细胞的消除引发了毛细血管扩张、血流量增加和血管舒张受损，这表明通过PANX1通道释放的嘌呤在激活小胶质P2RY12受体以调节神经血管结构和功能方面发挥了重要作用。小胶质细胞参与碎片清除和突触修剪等过程。然而，它们与脑血管系统的直接相互作用尚不清楚。在这里，作者表明毛细血管相关小胶质细胞（CAMs）通过PANX1-P2RY12信号调节血管张力。
Microglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 + myeloid cell somata and brain capillaries. We confirm that these cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then, we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing them with parenchymal microglia (PCMs) in their morphological activities including during microglial depletion and repopulation. Molecularly, we identify P2RY12 receptors as a regulator of CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, microglial elimination triggered capillary dilation, blood flow increase, and impaired vasodilation that were recapitulated in P2RY12−/− and PANX1−/− mice suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function. Microglia are involved in debris clearance and synaptic pruning, among other processes. However, their direct interaction with the brain vasculature is less clear. Here, the authors show that capillary-associated microglia (CAMs) regulate vascular tone via PANX1-P2RY12 signalling.
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影响因子：
30.5
作者：
Goldmann T;Wieghofer P;Jordão MJ;Prutek F;Hagemeyer N;Frenzel K;Amann L;Staszewski O;Kierdorf K;Krueger M;Locatelli G;Hochgerner H;Zeiser R;Epelman S;Geissmann F;Priller J;Rossi FM;Bechmann I;Kerschensteiner M;Linnarsson S;Jung S;Prinz M
通讯作者：
Prinz M
影响因子：
6.2
作者：
Eyo, Ukpong;Dailey, Michael E.
通讯作者：
Dailey, Michael E.
影响因子：
5.3
作者：
Avignone, Elena;Ulmann, Lauriane;Audinat, Etienne
通讯作者：
Audinat, Etienne
影响因子：
3.4
作者：
Bowyer, John F.;Sarkar, Sumit;Hanig, Joseph P.
通讯作者：
Hanig, Joseph P.
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana