The brain-immune ecosystem: Implications for immunotherapy in defeating neurodegenerative diseases

Schwartz, Michal; Abellanas, Miguel A.; Tsitsou-Kampeli, Afroditi; Suzzi, Stefano

doi:10.1016/j.neuron.2022.09.007

Cited by 14 publications

(7 citation statements)

References 13 publications

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“…Under homeostatic conditions, it is now clear that the adaptive immune system is present. Though low in levels, adaptive immune cells, including T cells and B cells, can enter the brain meninges, occupy the dura through skull channels—and play crucial roles in brain maintenance, including neuronal function, brain development, and spatial learning [ 152 ], mainly due to cytokines released from T cells, including interleukin-4 (IL-4), IL-17, and IFN-γ [ 153 ]. It has been shown that a deficiency of IL-4-producing T cells in the meninges [ 154 ] or an excess of these cells in choroid plexus during aging [ 155 ] negatively impacts the brain, emphasizing the importance of the adaptive immune system contributing to brain function and maintenance during homeostatic conditions.…”

Section: Neuroimmune Alterations In Admentioning

confidence: 99%

“…Similarly, lower levels of IFN-γ in the plasma of AD patients were associated with progression of cognitive deficiency [ 157 ]. While the underlying mechanisms of increased infiltration of adaptive immune cells in neurodegenerative diseases and aging remain to be elucidated, the role of infiltrating T cells on disease progression differs extensively depending on the specific neurodegenerative disease under investigation and their functional programming [ 153 ]. In this section, we summarize the current status of research on the role of innate and adaptive immunity and crosstalk between these systems (Fig.…”

Section: Neuroimmune Alterations In Admentioning

confidence: 99%

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The neuroimmune axis of Alzheimer’s disease

2023

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Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder with multifaceted neuropathological features, including β-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Over the past decade, emerging evidence has implicated both beneficial and pathological roles for innate immune genes and immune cells, including peripheral immune cells such as T cells, which can infiltrate the brain and either ameliorate or exacerbate AD neuropathogenesis. These findings support a neuroimmune axis of AD, in which the interplay of adaptive and innate immune systems inside and outside the brain critically impacts the etiology and pathogenesis of AD. In this review, we discuss the complexities of AD neuropathology at the levels of genetics and cellular physiology, highlighting immune signaling pathways and genes associated with AD risk and interactions among both innate and adaptive immune cells in the AD brain. We emphasize the role of peripheral immune cells in AD and the mechanisms by which immune cells, such as T cells and monocytes, influence AD neuropathology, including microglial clearance of amyloid-β peptide, the key component of β-amyloid plaque cores, pro-inflammatory and cytotoxic activity of microglia, astrogliosis, and their interactions with the brain vasculature. Finally, we review the challenges and outlook for establishing immune-based therapies for treating and preventing AD.

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Section: Neuroimmune Alterations In Admentioning

confidence: 99%

Section: Neuroimmune Alterations In Admentioning

confidence: 99%

The neuroimmune axis of Alzheimer’s disease

2023

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“…Recent work by Schwartz et al (2022) proposed the idea of a brain-immune network “ecosystem.” The received view considered indeed the brain as a self-contained tissue responsible for its own immune protection and equipped with microglia, acting as internal immune sentinels. However, as Shechter et al (2013) note, the Central Nervous System (CNS) repair and higher brain function ( Ziv et al, 2006 ) have been found to be dependent on adaptive and innate immune cells derived from the circulation.…”

Section: The Brain-immune Networkmentioning

confidence: 99%

“…The brain-immune network “ecosystem” consists of the idea that “the cellular elements of this immunological network, together with the non-immune cells of the brain—neurons, astrocytes, and oligodendrocytes—constitute a functional structure with properties of an “ecosystem,” characterized by interdependent compartments of immune cells that interact with each other within a physically connected microenvironment, thereby contributing to increased stability and resilience of the CNS in the face of continuous disruption in its day-to- day activities.” [ Schwartz et al (2022) :1].…”

Section: The Brain-immune Networkmentioning

confidence: 99%

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The brain is not mental! coupling neuronal and immune cellular processing in human organisms

Ciaunica

Shmeleva

Levin

2023

Front. Integr. Neurosci.

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Significant efforts have been made in the past decades to understand how mental and cognitive processes are underpinned by neural mechanisms in the brain. This paper argues that a promising way forward in understanding the nature of human cognition is to zoom out from the prevailing picture focusing on its neural basis. It considers instead how neurons work in tandem with other type of cells (e.g., immune) to subserve biological self-organization and adaptive behavior of the human organism as a whole. We focus specifically on the immune cellular processing as key actor in complementing neuronal processing in achieving successful self-organization and adaptation of the human body in an ever-changing environment. We overview theoretical work and empirical evidence on “basal cognition” challenging the idea that only the neuronal cells in the brain have the exclusive ability to “learn” or “cognize.” The focus on cellular rather than neural, brain processing underscores the idea that flexible responses to fluctuations in the environment require a carefully crafted orchestration of multiple cellular and bodily systems at multiple organizational levels of the biological organism. Hence cognition can be seen as a multiscale web of dynamic information processing distributed across a vast array of complex cellular (e.g., neuronal, immune, and others) and network systems, operating across the entire body, and not just in the brain. Ultimately, this paper builds up toward the radical claim that cognition should not be confined to one system alone, namely, the neural system in the brain, no matter how sophisticated the latter notoriously is.

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