Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders

Zengeler, Kristine E.; Lukens, John R.

doi:10.1038/s41577-020-00487-7

Cited by 157 publications

(145 citation statements)

References 241 publications

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“…This is not only important during early developmental stages as depleting microglia from the CNS of adult mice also results in impaired synaptic plasticity and deficits in learning and memory (13,(40)(41)(42). Similar phenotypes are observed when microglia are unable to produce brain-derived neurotrophic factor (BDNF), as shown using conditional and inducible BDNF depletion under the CX 3 CR1 promotor (42) Thus, although microglia have several well-defined roles in neuroinflammation, it is becoming increasingly evident that they also shape neuronal survival and connectivity during development, interpret changes in the local milieu and modulate circuit formation accordingly (11,43).…”

Section: Microglia: Origin and Physiological Functions In The Brainmentioning

confidence: 90%

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Microbiota and Microglia Interactions in ASD

2021

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Autism spectrum disorders (ASD) are serious, highly variable neurodevelopmental disorders, commonly characterized by the manifestation of specific behavioral abnormalities, such as stereotypic behaviors and deficits in social skills, including communication. Although the neurobiological basis for ASD has attracted attention in recent decades, the role of microglial cells, which are the main resident myeloid cell population in the brain, is still controversial and underexplored. Microglia play several fundamental roles in orchestrating brain development and homeostasis. As such, alterations in the intrinsic functions of these cells could be one of the driving forces responsible for the development of various neurodevelopmental disorders, including ASD. Microglia are highly sensitive to environmental cues. Amongst the environmental factors known to influence their intrinsic functions, the gut microbiota has emerged as a central player, controlling both microglial maturation and activation. Strikingly, there is now compelling data suggesting that the intestinal microbiota can play a causative role in driving the behavioural changes associated with ASD. Not only is intestinal dysbiosis commonly reported in ASD patients, but therapies targeting the microbiome can markedly alleviate behavioral symptoms. Here we explore the emerging mechanisms by which altered microglial functions could contribute to several major etiological factors of ASD. We then demonstrate how pre- and postnatal environmental stimuli can modulate microglial cell phenotype and function, underpinning the notion that reciprocal interactions between microglia and intestinal microbes could play a crucial role in ASD aetiology.

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Section: Microglia: Origin and Physiological Functions In The Brainmentioning

confidence: 90%

“…Thus, although microglia have several well-defined roles in neuroinflammation, it is becoming increasingly evident that they also shape neuronal survival and connectivity during development, interpret changes in the local milieu and modulate circuit formation accordingly ( 11 , 43 ).…”

Section: Microglia: Origin and Physiological Functions In The Brainmentioning

confidence: 99%

Microbiota and Microglia Interactions in ASD

2021

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“…Despite these exciting recent advances, further research is needed to determine the most ideal time point(s) to implement this depletion/repopulation microglia strategy and to also uncover additional molecular players mechanistically orchestrating beneficial or detrimental microglia functions following head trauma. Moreover, given the prominent role that microglia play in shaping neurodevelopment [31,32,34,78], it will also be important to carefully evaluate how microglia depletion approaches affect TBI in different age groups, especially in the young.…”

Section: Glossarymentioning

confidence: 99%

Neuroimmune cleanup crews in brain injury

Bolte

Lukens

2021

Trends in Immunology

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“…Microglia enter the CNS early in embryogenesis and maintain their CNS population by self-renewal, constituting 5–10% of total brain cells [ 12 ]. Microglia play important roles in neurodevelopment, synaptic remodeling, and phagocytosis of unwanted cells [ 13 ]. They also scan the entire brain parenchyma every few hours, sensing ATP to respond to CNS damage [ 14 ].…”

Section: The Immune Landscapes Of Glioblastomamentioning

confidence: 99%

“…This stringent partitioning initially misled researchers to believe that the CNS was “immune privileged”, which is a hypothesis that has since been disproven [ 13 , 18 , 19 , 20 , 21 ]. The segregation of the brain parenchyma and peripheral immunity is not unalterable; rather, there is flexibility in this separation driven by disease [ 15 ].…”

Section: The Immune Landscapes Of Glioblastomamentioning

confidence: 99%

The Role of NKT Cells in Glioblastoma

Brettschneider

Terabe

2021

Cells

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Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.

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Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders

Cited by 157 publications

References 241 publications

Microbiota and Microglia Interactions in ASD

Microbiota and Microglia Interactions in ASD

Neuroimmune cleanup crews in brain injury

The Role of NKT Cells in Glioblastoma

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