Th1 Polarization of T Cells Injected into the Cerebrospinal Fluid Induces Brain Immunosurveillance

Fisher, Yair; Strominger, Itai; Biton, Shva; Nemirovsky, Anna; Baron, Rona; Monsonego, Alon

doi:10.4049/jimmunol.1301707

Cited by 55 publications

(48 citation statements)

References 54 publications

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“…Depletion of regulatory T (Treg) cells in an AD mouse model accelerated the onset of cognitive deficits without altering brain Aβ load (Dansokho et al , 2016). Administration of Aβ-specific type 1 T helper (Th1) cells into the brain lateral ventricle of an AD mouse model enhanced removal of cerebral Aβ deposits and promoted neurogenesis without harmful effects (Fisher et al , 2014). Thus, these T cells play beneficial roles in the AD pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer’s disease

Yang

Kou

Lalonde

et al. 2017

Brain, Behavior, and Immunity

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Neuroinflammation is a pervasive feature of Alzheimer’s disease (AD) and characterized by activated microglia, increased proinflammatory cytokines and/or infiltrating immune cells. T helper 17 (Th17) cells are found in AD brain parenchyma and interleukin-17A (IL-17A) is identified around deposits of aggregated amyloid β protein (Aβ). However, the role of IL-17A in AD pathogenesis remains elusive. We overexpressed IL-17A in an AD mouse model via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated intracranial gene delivery. AD model mice subjected to injection of a vehicle (PBS) or rAAV5 carrying the lacZ gene served as controls. IL-17A did not exacerbate neuroinflammation in IL-17A-overexpressing mice. We found that IL-17A overexpression markedly improved glucose metabolism, decreased soluble Aβ levels in the hippocampus and cerebrospinal fluid, drastically reduced cerebral amyloid angiopathy, and modestly but significantly improved anxiety and learning deficits. Moreover, the ATP-binding cassette subfamily A member 1 (ABCA1), which can transport Aβ from the brain into the blood circulation, significantly increased in IL-17A-overexpressing mice. In vitro treatment of brain endothelial bEnd.3 cells with IL-17A induced a dose-dependent increase in protein expression of ABCA1 through ERK activation. Our study suggests that IL-17A may decrease Aβ levels in the brain by upregulating ABCA1 in blood-brain barrier endothelial cells.

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Section: Introductionmentioning

confidence: 99%

Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer’s disease

Yang

Kou

Lalonde

et al. 2017

Brain, Behavior, and Immunity

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“…In fact, there are huge discrepancies with respect to cytokine production from Th1 or Th2 cells and the ratio of Th1/Th2 cells can even affect stroke severity . Th17 cells and γδ T cells produce pro‐inflammatory cytokines and chemokines, usually impairing neurogenesis . However, it is recently suggested that IL‐17A secreted by γδ T cells unexpectedly promoted neuronal differentiation via p38 mitogen‐activated protein kinase in cultured NPCs .…”

Section: The Role Of Neuroinflammation In Multiple Brain Repair Mechamentioning

confidence: 99%

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

et al. 2018

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Stroke is the world's leading cause of disability with limited brain repair treatments which effectively improve long-term neurological deficits. The neuroinflammatory responses persist into the late repair phase of stroke and participate in all brain repair elements, including neurogenesis, angiogenesis, synaptogenesis, remyelination and axonal sprouting, shedding new light on post-stroke brain recovery. Resident brain glial cells, such as astrocytes not only contribute to neuroinflammation after stroke, but also secrete a wide range of trophic factors that can promote post-stroke brain repair. Alternatively, activated microglia, monocytes, and neutrophils in the innate immune system, traditionally considered as major damaging factors after stroke, have been suggested to be extensively involved in brain repair after stroke. The adaptive immune system may also have its bright side during the late regenerative phase, affecting the immune suppressive regulatory T cells and B cells. This review summarizes the recent findings in the evolving role of neuroinflammation in multiple post-stroke brain repair mechanisms and poses unanswered questions that may generate new directions for future research and give rise to novel therapeutic targets to improve stroke recovery.

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“…In the same mouse model of AD, Aβ-specific Th1 cells were intracerebroventricularly injected into the Cerebrial spinal fluid of APP/PS1 mice, and showed to target Aβ plaques that resulted in reduction of Aβ plaque load and slight enhancement of neurogenesis [54]. This dichotomous role of Th1 cells in Alzheimer's Disease indicates that the route of migration (localization) and temporal factors may play a role in whether antigen-specific Th1 cells are beneficial or detrimental in neuro-degeneration.…”

Section: T Cell Subsets and Consensual Roles In Neural De/re-generatimentioning

confidence: 99%

Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging

Coder

Wang

et al. 2016

Oncotarget

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The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and “protective autoimmunity” provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the “thymus-inflammaging-neurodegeneration axis”.

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Th1 Polarization of T Cells Injected into the Cerebrospinal Fluid Induces Brain Immunosurveillance

Cited by 55 publications

References 54 publications

Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer’s disease

Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer’s disease

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging

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