Boulay Anne-Cécile, Mazeraud Aurélien, Cisternino Salvatore, Saubaméa Bruno, Mailly Phillipe, Jourdren Laurent, Blugeon Corinne, Mignon Virginie, Smirnova Maria, Cavallo Alessia, Ezan Pascal, Avé Patrick, Dingli Florent, Loew Damarys, Vieira Paulo, Chrétien Fabrice, Cohen-Salmon Martine
College of France, Center for Interdisciplinary Research in Biology/National Center of Scientific Research (CNRS), Coeducational Research Unit (UMR) 7241, National Institute of Health and Medical Research (INSERM), U1050/Neuroglial Interactions in Cerebral Physiopathology, F-75231 Paris, France, University Pierre and Marie Curie, F-75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, F-75005 Paris, France.
Human Histopathology and Animal Models and Paris Descartes University-Sorbonne Paris Cité and Neuropathology Service, Sainte-Anne Hospital Center, F-75014 Paris, France.
J Neurosci. 2015 Mar 11;35(10):4427-39. doi: 10.1523/JNEUROSCI.2575-14.2015.
In the normal brain, immune cell trafficking and immune responses are strictly controlled and limited. This unique homeostatic equilibrium, also called brain immune quiescence, is crucial to maintaining proper brain functions and is altered in various pathological processes, from chronic immunopathological disorders to cognitive and psychiatric impairments. To date, the precise nature of factors regulating the brain/immune system interrelationship is poorly understood. In the present study, we demonstrate that one of these regulating factors is Connexin 43 (Cx43), a gap junction protein highly expressed by astrocytes at the blood-brain barrier (BBB) interface. We show that, by setting the activated state of cerebral endothelium, astroglial Cx43 controls immune recruitment as well as antigen presentation mechanisms in the mouse brain. Consequently, in the absence of astroglial Cx43, recruited immune cells elaborate a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein of the brain. Altogether, our results demonstrate that Cx43 is a new astroglial factor promoting the immune quiescence of the brain.
在正常大脑中，免疫细胞的运输和免疫反应受到严格控制和限制。这种独特的稳态平衡，也称为脑免疫静止，对于维持大脑正常功能至关重要，并且在从慢性免疫病理疾病到认知和精神障碍的各种病理过程中都会发生改变。迄今为止，调节脑/免疫系统相互关系的因素的确切性质仍知之甚少。在本研究中，我们证明其中一个调节因素是连接蛋白43（Cx43），它是一种在血脑屏障（BBB）界面处由星形胶质细胞高度表达的间隙连接蛋白。我们表明，通过设定脑内皮的激活状态，星形胶质细胞Cx43控制小鼠大脑中的免疫募集以及抗原呈递机制。因此，在没有星形胶质细胞Cx43的情况下，募集的免疫细胞会针对含血管性血友病因子A结构域蛋白5a（一种大脑的细胞外基质蛋白）产生特异性体液自身免疫反应。总之，我们的结果表明Cx43是一种促进大脑免疫静止的新的星形胶质细胞因子。
