Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes

Sanmarco, Liliana M.; Wheeler, Michael A.; Gutiérrez-Vázquez, Cristina; Polonio, Carolina Manganeli; Linnerbauer, Mathias; Pinho‐Ribeiro, Felipe A.; Li, Zhaorong; Giovannoni, Federico; Batterman, Katelyn V.; Scalisi, Giulia; Zandee, Stéphanie; Heck, Evelyn S.; Alsuwailm, Moneera; Rosene, Douglas L.; Becher, Burkhard; Chiu, Isaac M.; Prat, Alexandre; Quintana, Francisco J.

doi:10.1038/s41586-020-03116-4

Cited by 222 publications

(182 citation statements)

References 92 publications

(140 reference statements)

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“…Using these complementary models, we demonstrated a protective effect of NK cells on recovery of motor behavior in vivo . It was shown that NK cells induce homeostatic anti-inflammatory activities of astrocytes via IFN-γ (Hindinger et al, 2012; Sanmarco et al, 2021). Indeed, astrocytes were found to be activated in ischemic stroke already at P3 (Werner et al, 2020), at the same time when the effect of NK cell absence was observed in our beam-walk sensorimotor test.…”

Section: Discussionmentioning

confidence: 99%

Brain endothelial CXCL12 attracts protective Natural Killer cells during ischemic stroke

Wang

Fabritus

Kumar

et al. 2021

Preprint

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Innate lymphoid cells (ILCs) have a function in homeostasis and immune responses, but their role in ischemic brain insult is unknown. Here, we report that ILCs are not resident within the brain parenchyma during steady-state conditions, but are attracted after ischemic stroke. Specifically, we identified NK cells, ILC1s, ILC2s and ILC3s within the lesion, the highest influx being observed for NK cells and ILC1s. We further show that Cxcl12 expressed at the blood-brain barrier is essential for NK cells and NKp46+ ILC3s to migrate toward the lesion. Complementary, Cxcr4-deficiency in NK cells prevented NK cells from entering the infarct area. The lack of NK cell migration resulted in a higher neurological deficit in the beam-walk sensorimotor test. Our data show a new role for blood-brain barrier-derived Cxcl12 in attracting protective NK cells to ischemic brain lesions and identifies a new Cxcl12/ Cxcr4-mediated component of the innate immune response to stroke.

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Section: Discussionmentioning

confidence: 99%

Brain endothelial CXCL12 attracts protective Natural Killer cells during ischemic stroke

Wang

Fabritus

Kumar

et al. 2021

Preprint

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“…Very recently, it was demonstrated by a high-speed flow cytometry screening experiment, single-cell RNA sequencing, and CRISPR–Cas9-based cell-specific in vivo genetic disturbances in mice that there is a set of astrocytes in the central nervous system that can limit inflammation by inducing T-cell apoptosis, receiving signals from the gut bacteria that stimulate anti-inflammatory activity under the action of interferon-γ (IFNγ) produced by natural killer meningeal cells, in which IFNγ expression is modulated by the intestinal microbiome [ 272 ].…”

Section: Photobiomodulation Applied On the Gut–lung–brain Axismentioning

confidence: 99%

Probiotics, Photobiomodulation, and Disease Management: Controversies and Challenges

Ailioaie

Litscher

2021

IJMS

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In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut–lung–brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.

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“…For example, Wheeler et al [ 37 ] showed that reduced astrocyte expression of the Nuclear factor erythroid 2-related factor 2 (NRF2) was correlated with increased production of the small musculoaponeurotic fibrosarcoma G (MAFG) proteins that enhance the inflammatory responses of infiltrating T-cells in EAE mouse models. The same research group showed that astrocytes expressing high levels of lysosome-associated membrane protein 1 (LAMP-1) and the TNF-related apoptosis-inducing ligand (TRAIL) promoted apoptosis of infiltrating T-cells, thus performing an anti-inflammatory activity [ 131 ]. On the other hand, astrocyte expression of these markers was found to depend on their interactions with infiltrating NK cells, secreting the cytokine IFN-γ, and was inhibited by other cytokines such as tumor necrosis factor (TNF) and interleukin 1α (IL-1α), secreted by T cells.…”

Section: Astrocytesmentioning

confidence: 99%

Neuroinflammation: Integrated Nervous Tissue Response through Intercellular Interactions at the “Whole System” Scale

Nosi

Lana

Giovannini

et al. 2021

Cells

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Different cell populations in the nervous tissue establish numerous, heterotypic interactions and perform specific, frequently intersecting activities devoted to the maintenance of homeostasis. Microglia and astrocytes, respectively the immune and the “housekeeper” cells of nervous tissue, play a key role in neurodegenerative diseases. Alterations of tissue homeostasis trigger neuroinflammation, a collective dynamic response of glial cells. Reactive astrocytes and microglia express various functional phenotypes, ranging from anti-inflammatory to pro-inflammatory. Chronic neuroinflammation is characterized by a gradual shift of astroglial and microglial phenotypes from anti-inflammatory to pro-inflammatory, switching their activities from cytoprotective to cytotoxic. In this scenario, the different cell populations reciprocally modulate their phenotypes through intense, reverberating signaling. Current evidence suggests that heterotypic interactions are links in an intricate network of mutual influences and interdependencies connecting all cell types in the nervous system. In this view, activation, modulation, as well as outcomes of neuroinflammation, should be ascribed to the nervous tissue as a whole. While the need remains of identifying further links in this network, a step back to rethink our view of neuroinflammation in the light of the “whole system” scale, could help us to understand some of its most controversial and puzzling features.

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Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes

Cited by 222 publications

References 92 publications

Brain endothelial CXCL12 attracts protective Natural Killer cells during ischemic stroke

Brain endothelial CXCL12 attracts protective Natural Killer cells during ischemic stroke

Probiotics, Photobiomodulation, and Disease Management: Controversies and Challenges

Neuroinflammation: Integrated Nervous Tissue Response through Intercellular Interactions at the “Whole System” Scale

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