IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair

Kunis, Gilad; Baruch, Kuti; Rosenzweig, Neta; Kertser, Alexander; Miller, Omer; Berkutzki, Tamara; Schwartz, Michal

doi:10.1093/brain/awt259

Cited by 266 publications

(299 citation statements)

References 54 publications

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“…6). In the absence of neuroinflammation local activation of CNS-specific Th1 and Th2 cells induces expression of the Th1 and Th2 signature cytokines, IFN-γ and IL-4, which may maintain expression of trafficking molecules at the choroid plexus allowing for limited T cell trafficking into the ventricles [10,75]. The choroidal endothelium, fenestrated and thus permissive to large molecules, does not display a BBB phenotype.…”

Section: Neuroimmune Function Of the Choroid Plexuses In Healthmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

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Section: Neuroimmune Function Of the Choroid Plexuses In Healthmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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“…29,30 In addition, there is evidence showing the presence of CNS-specific T cells located within the choroid plexus that promotes leukocyte trafficking into the CNS after injury. 31,32 Approximately 15% of these choroid plexus T cells are CD4…”

Section: Inflammation In the Mammalian Brainmentioning

confidence: 99%

Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

Tobin

Bonds

Minshall

et al. 2014

J Cereb Blood Flow Metab

298

236

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This review covers the pathogenesis of ischemic stroke and future directions regarding therapeutic options after injury. Ischemic stroke is a devastating disease process affecting millions of people worldwide every year. The mechanisms underlying the pathophysiology of stroke are not fully understood but there is increasing evidence demonstrating the contribution of inflammation to the drastic changes after cerebral ischemia. This inflammation not only immediately affects the infarcted tissue but also causes long-term damage in the ischemic penumbra. Furthermore, the interaction between inflammation and subsequent neurogenesis is not well understood but the close relationship between these two processes has garnered significant interest in the last decade or so. Current approved therapy for stroke involving pharmacological thrombolysis is limited in its efficacy and new treatment strategies need to be investigated. Research aimed at new therapies is largely about transplantation of neural stem cells and using endogenous progenitor cells to promote brain repair. By understanding the interaction between inflammation and neurogenesis, new potential therapies could be developed to further establish brain repair mechanisms.

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“…75 Like the endothelial cells of the BBB, the CPE cells express tight junctions and serve as a barrier to separate the CNS from the circulation, and the migration across the BCSFB is restricted. However, monocytes 76,77 and T cells 78 have been shown to enter the CNS via the BCSFB in response to injury. It is known that JCPyV entry 5-HT 2 receptors are expressed in the CPE 79,80 and that 5-HT 2C isolated from the rat choroid plexus is N-glycosylated.…”

Section: Direct Binding Of Jcpyv To Barriers Of the Cnsmentioning

confidence: 99%

Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

Haley

O’Hara

Nelson

et al. 2015

The American Journal of Pathology

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The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy, a rare demyelinating disease that occurs in the setting of prolonged immunosuppression. After initial asymptomatic infection, the virus establishes lifelong persistence in the kidney and possibly other extraneural sites. In rare instances, the virus traffics to the central nervous system, where oligodendrocytes, astrocytes, and glial precursors are susceptible to lytic infection, resulting in progressive multifocal leukoencephalopathy. The mechanisms by which the virus traffics to the central nervous system from peripheral sites remain unknown. Lactoseries tetrasaccharide c (LSTc), a pentasaccharide containing a terminal a2,6elinked sialic acid, is the major attachment receptor for polyomavirus. In addition to LSTc, type 2 serotonin receptors are required for facilitating virus entry into susceptible cells. We studied the distribution of virus receptors in kidney and brain using lectins, antibodies, and labeled virus. The distribution of LSTc, serotonin receptors, and virus binding sites overlapped in kidney and in the choroid plexus. In brain parenchyma, serotonin receptors were expressed on oligodendrocytes and astrocytes, but these cells were negative for LSTc and did not bind virus. LSTc was instead found on microglia and vascular endothelium, to which virus bound abundantly. Receptor distribution was not changed in the brains of patients with progressive multifocal leukoencephalopathy. Virus infection of oligodendrocytes and astrocytes during disease progression is LSTc independent. (Am J Pathol 2015, 185: 2246e2258; http://dx.doi.org/10.1016/j.ajpath.2015.04.003)The human polyomavirus (JCPyV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a rapidly progressing, often fatal neurodegenerative disease. Although PML is rare, JCPyV infection is widespread, infecting approximately 50% to 80% of the healthy adult population. 1,2 As the initial infection is asymptomatic, the mode of JCPyV transmission is unknown. The virus establishes a persistent infection in the kidney and urinary tract of immunocompetent hosts, 3 and about 20% of these infected individuals shed virus in their urine. 4 JCPyV DNA has also been detected in other tissues, including B lymphocytes in the bone marrow, tonsillar stromal cells, lungs, spleen, and brain, 5e13 suggesting additional sites of viral persistence. The route of viral transmission from the initial site(s) of infection and latency to the central nervous system (CNS), the main site of pathogenesis, is not clearly understood.Under conditions of immunosuppression, JCPyV infects and destroys the myelin-producing oligodendrocytes, resulting in demyelination, which is the hallmark of this fatal disease; to a Supported by NIH grants R01NS043097 (W.J.A.) and P01NS065719 (W.J.A.).

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IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair

Cited by 266 publications

References 54 publications

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

Human Polyomavirus Receptor Distribution in Brain Parenchyma Contrasts with Receptor Distribution in Kidney and Choroid Plexus

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