The Expression Patterns of MHC Class I Molecules in the Developmental Human Visual System

Zhang, Aifeng; Yu, Hong; Shen, Yuqing; Liu, Jiane; He, Yao; Shi, Qian; Fu, Bo; Miao, Fengqin; Zhang, Jianqiong

doi:10.1007/s11064-012-0916-9

Cited by 18 publications

(18 citation statements)

References 47 publications

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“…In the LGN, β2m was observed at 29–31 gestational weeks but, was nearly absent by postnatal day 55, and was completely absent in the adult 22 . MHC-I in the human visual cortex was not observed at any gestational or postnatal stage 22 , while the expression of MHC-I was very low in the hippocampus at 20 gestational weeks and slowly increased during weeks 27–33. A rapid increase in MHC-I molecule expression was found in the subiculum that reached high levels at 31–33 gestational weeks, but no expression of MHC-I was found in the adult hippocampus 23 .…”

Section: Introductionmentioning

confidence: 97%

“…The first was a study of a childhood viral infection, Rasmussen’s encephalitis, in which immunolabel for the MHC-I component, beta 2 microglobulin (β2m), was present in cortical and hippocampal neurons 20 ; more recently, MHC-I has also been observed in dysmorphic/dysphasic cortical neurons of focal cortical dysplasia, tuberous sclerosis complex and ganglioglioma cases 21 and in the embryonic LGN of the dorsal thalamus 22 and hippocampus 23 . In the LGN, β2m was observed at 29–31 gestational weeks but, was nearly absent by postnatal day 55, and was completely absent in the adult 22 . MHC-I in the human visual cortex was not observed at any gestational or postnatal stage 22 , while the expression of MHC-I was very low in the hippocampus at 20 gestational weeks and slowly increased during weeks 27–33.…”

Section: Introductionmentioning

confidence: 99%

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MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

et al. 2014

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Subsets of rodent neurons are reported to express major histocompatibilty complex class I (MHC-I), but such expression has not been reported in normal adult human neurons. Here we provide evidence from immunolabel, RNA expression, and mass spectrometry analysis of postmortem samples that human catecholaminergic substantia nigra and locus coeruleus neurons express MHC-I, and that this molecule is inducible in human stem cell derived dopamine (DA) neurons. Catecholamine murine cultured neurons are more responsive to induction of MHC-I by gamma-interferon than other neuronal populations. Neuronal MHC-I is also induced by factors released from microglia activated by neuromelanin or alpha-synuclein, or high cytosolic DA and/or oxidative stress. DA neurons internalize foreign ovalbumin and display antigen derived from this protein by MHC-I, which triggers DA neuronal death in the presence of appropriate cytotoxic T-cells. Thus, neuronal MHC-I can trigger antigenic response, and catecholamine neurons may be particularly susceptible to T cell-mediated cytotoxic attack.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

et al. 2014

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“…We have proposed that this mechanism underlies the injury of demyelinated axons in multiple sclerosis (MS) 1, 2, 4, 10. Evidence also suggests that MHC I is involved with synaptic pruning during cortical development12, 13, 14, 16, 17, 18, 19, 20, 21 and following injury22, 23, 24, 25 and contributes to neuronal plasticity 16, 17, 26, 27. These findings also suggest that retrogradely induced MHC class I may contribute to the diffuse synaptopathy observed in MS and other neurodegenerative diseases 28, 29, 30, 31, 32, 33, 34, 35.…”

Section: Introductionmentioning

confidence: 99%

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

Clarkson

Patel

LaFrance‐Corey

et al. 2017

Ann Clin Transl Neurol

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ObjectiveInjury‐associated axon‐intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN γ) signals are known to induce expression of major histocompatibility class I (MHC I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen‐specific CD8+ T cells. We sought to determine whether the same is true in human neurons.MethodsA novel microisolation chamber design was used to physically isolate and manipulate axons from human skin fibroblast‐derived induced pluripotent stem cell (iPSC)‐derived neuron‐enriched neural aggregates. Fluorescent retrobeads were used to assess the fraction of neurons with projections to the distal chamber. Axons were treated with IFN γ for 72 h and expression of MHC class I and antigen presentation genes were evaluated by RT‐PCR and immunofluorescence.ResultsHuman iPSC‐derived neural stem cells maintained as 3D aggregate cultures in the cell body chamber of polymer microisolation chambers extended dense axonal projections into the fluidically isolated distal chamber. Treatment of these axons with IFN γ resulted in upregulation of MHC class I and antigen processing genes in the neuron cell bodies. IFN γ‐induced MHC class I molecules were also anterogradely transported into the distal axon.InterpretationThese results provide conclusive evidence that human axons are competent to express MHC class I molecules, suggesting that inflammatory factors enriched in demyelinated lesions may render axons vulnerable to attack by autoreactive CD8+ T cells in patients with MS. Future work will be aimed at identifying pathogenic anti‐axonal T cells in these patients.

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“…MHCI proteins are expressed in a brain tissue-specific and developmental stage-specific manner (Liu et al, 2013;Zhang et al, 2013a), and may be major actors in developmental synaptic pruning, which is dependent on neuronal activity (Glynn et al, 2011;Lee et al, 2014). MHCI proteins are particularly expressed in neurons of the lateral geniculate nucleus of the thalamus (Zhang et al, 2013b), and also affect axonal and neurite outgrowth of hippocampal neurons in vitro (Bilousova et al, 2012). In addition, knock-out mice for the homologous immune system show increased ocular dominance, as well as aberrant patterns of Long-Term Potentiation (LTP) and Long-Term Depression (LTD) in the hippocampus (Datwani et al, 2009;Elmer and McAllister, 2012;Huh et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

A schizophrenia-associated HLA locus affects thalamus volume and asymmetry

Brucato

Guadalupe

Franke

et al. 2015

Brain, Behavior, and Immunity

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a b s t r a c tGenes of the Major Histocompatibility Complex (MHC) have recently been shown to have neuronal functions in the thalamus and hippocampus. Common genetic variants in the Human Leukocyte Antigens (HLA) region, human homologue of the MHC locus, are associated with small effects on susceptibility to schizophrenia, while volumetric changes of the thalamus and hippocampus have also been linked to schizophrenia. We therefore investigated whether common variants of the HLA would affect volumetric variation of the thalamus and hippocampus. We analysed thalamus and hippocampus volumes, as measured using structural magnetic resonance imaging, in 1.265 healthy participants. These participants had also been genotyped using genome-wide single nucleotide polymorphism (SNP) arrays. We imputed genotypes for single nucleotide polymorphisms at high density across the HLA locus, as well as HLA allotypes and HLA amino acids, by use of a reference population dataset that was specifically targeted to the HLA region. We detected a significant association of the SNP rs17194174 with thalamus volume (nominal P = 0.0000017, corrected P = 0.0039), as well as additional SNPs within the same region of linkage disequilibrium. This effect was largely lateralized to the left thalamus and is localized within a genomic region previously associated with schizophrenia. The associated SNPs are also clustered within a potential regulatory element, and a region of linkage disequilibrium that spans genes expressed in the thalamus, including HLA-A. Our data indicate that genetic variation within the HLA region influences the volume and asymmetry of the human thalamus. The molecular mechanisms underlying this association may relate to HLA influences on susceptibility to schizophrenia.

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The Expression Patterns of MHC Class I Molecules in the Developmental Human Visual System

Cited by 18 publications

References 47 publications

MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

A schizophrenia-associated HLA locus affects thalamus volume and asymmetry

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