The transcription factor nuclear factor κB（NF-κB） plays major roles in inflammatory diseases through regulation of inflammation and cell viability.Multiple sclerosis（MS） is a chronic inflammatory demyelinating a...The transcription factor nuclear factor κB（NF-κB） plays major roles in inflammatory diseases through regulation of inflammation and cell viability.Multiple sclerosis（MS） is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system（CNS）.It has been shown that NF-κB is activated in multiple cell types in the CNS of MS patients,including T cells,microglia/macrophages,astrocytes,oligodendrocytes,and neurons.Interestingly,data from animal model studies,particularly studies of experimental autoimmune encephalomyelitis,have suggested that NF-κB activation in these individual cell types has distinct effects on the development of MS.In this review,we will cover the current literature on NF-κB and the evidence for its role in the development of MS and its animal model experimental autoimmune encephalomyelitis.展开更多
Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular funct...Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.展开更多
Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded ...Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded protein response can trigger apoptosis to eliminate stressed cells.Recent studies show that the unfolded protein response plays an important role in the pathogenesis of various disorders of myelin,including multiples sclerosis,Charcot-Marie-Tooth disease,Pelizaeus-Merzbacher disease,vanishing white matter disease,spinal cord injury,tuberous sclerosis complex,and hypoxia-induced perinatal white matter injury.In this review we summarize the current literature on the unfolded protein response and the evidence for its role in the pathogenesis of myelin disorders.展开更多
Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe n...Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.展开更多
The association of neurogenesis and gliogenesis with glioma remains unclear.By conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-O...The association of neurogenesis and gliogenesis with glioma remains unclear.By conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-OPC)-like and radial glia(RG)-like tumors and validated it in a public cohort and TCGA glioma.The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations,and the pri-OPC-like ones were prone to carrying TP53 mutations.Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes,suggesting their distinct immune evasion programs.Furthermore,the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners.Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes.For example,glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes,respectively.Their expression was positively correlated with those of immune checkpoint genes(e.g.,LGALS33)and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells.This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.展开更多
Multiple system atrophy(MSA)is a debilitating and fatal neurodegenerative disorder.The disease severity warrants urgent development of disease-modifying therapy,but the disease pathogenesis is still enigmatic.Neurodeg...Multiple system atrophy(MSA)is a debilitating and fatal neurodegenerative disorder.The disease severity warrants urgent development of disease-modifying therapy,but the disease pathogenesis is still enigmatic.Neurodegeneration in MSA brains is preceded by the emergence of glial cytoplasmic inclusions(GCIs),which are insoluble α-synuclein accumulations within oligodendrocytes(OLGs).Thus,preventive strategies against GCI formation may suppress disease progression.However,although numerous studies have tried to elucidate the molecular pathogenesis of GCI formation,difficulty remains in understanding the pathological interaction between the two pivotal aspects of GCIs;asynuclein and OLGs.The difficulty originates from several enigmas:1)what triggers the initial generation and possible propagation of pathogenic α-synuclein species?2)what contributes to OLG-specific accumulation of α-synuclein,which is abundantly expressed in neurons but not in OLGs?and 3)how are OLGs and other glial cells affected and contribute to neurodegeneration?The primary pathogenesis of GCIs may involve myelin dysfunaion and dyshomeostasis of the oligodendroglial cellular environment such as autophagy and iron metabolism.We have previously reported that oligodendrocyte precursor cells are more prone to develop intracellular inclusions in the presence of extracellular fibrillary α-synuclein.This finding implies a possibility that the propagation of GCI pathology in MSA brains is mediated through the internalization of pathological α-synuclein into oligodendrocyte precursor cells.In this review,in order to discuss the pathogenesis of GCIs,we will focus on the composition of neuronal and oligodendroglial inclusions in synucleinopathies.Furthermore,we will introduce some hypotheses on how α-synuclein pathology spreads among OLGs in MSA brains,in the light of our data from the experiments with primary oligodendrocyte lineage cell culture.While various reports have focused on the mysterious source of α-synuclein in GCIs,insights into the mecha展开更多
Methylprednisolone pulse treatment is currently used fo r optic neuritis.It can speed visual recovery,but does not improve the ultimate visual outcomes.Recent studies have repo rted that miR-125 a-5 p has immunomodula...Methylprednisolone pulse treatment is currently used fo r optic neuritis.It can speed visual recovery,but does not improve the ultimate visual outcomes.Recent studies have repo rted that miR-125 a-5 p has immunomodulatory effects on autoimmune diseases.However,it remains unclear whether miR-125 a-5 p has effects on optic neuritis.In this study,we used adeno-associated virus to overexpress or silence miR-125 a-5 p in mice.We found that silencing miR-125 a-5 p increased the latency of visual evoked potential and aggravated inflammation of the optic nerve.Ove rexpression of miR-125 a-5 p suppressed inflammation of the optic nerve,protected retinal ganglion cells,and increased the percentage of Treg cells.Our findings show that miR-125 a-5 p exhibits anti-inflammatory effects through promoting the diffe rentiation of Treg cells.展开更多
The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfo...The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.展开更多
Oligodendrocyte precursor cells(OPCs)are a heterogeneous multipotent population in the central nervous system(CNS)that appear during embryogenesis and persist as resident cells in the adult brain parenchyma.OPCs could...Oligodendrocyte precursor cells(OPCs)are a heterogeneous multipotent population in the central nervous system(CNS)that appear during embryogenesis and persist as resident cells in the adult brain parenchyma.OPCs could generate oligodendrocytes to participate in myelination.Recent advances have renewed our knowledge of OPC biology by discovering novel markers of oligodendroglial cells,the myelin-independent roles of OPCs,and the regulatory mechanism of OPC development.In this review,we will explore the updated knowledge on OPC identity,their multifaceted roles in the CNS in health and diseases,as well as the regulatory mechanisms that are involved in their developmental stages,which hopefully would contribute to a further understanding of OPCs and attract attention in the field of OPC biology.展开更多
Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating int...Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating into oligodendrocyte precursor cells(OPCs),before becoming immature oligodendrocytes,then mature oligodendrocytes(OLs).While the main function of cell lineage is in myelin formation,and increasing number of studies have turned to explore the immunological characteristics of these cells.Initially,these studies focused on discovering how OPCs and OLs are affected by the immune system,and then,how these immunological changes influence the myelination process.However,recent studies have uncovered another feature of OL-lineage cells in our immune systems.It would appear that OL-lineage cells also express immunological factors such as cytokines and chemokines in response to immune activation,and the expression of these factors changes under various pathologic conditions.Evidence suggests that OL-lineage cells actually modulate immune functions.Indeed,OL-lineage cells appear to play both"victim"and"agent"in the CNS which raises a number of questions.Here,we summarize immunologic changes in OL-lineage cells and their effects,as well as consider OL-lineage cell changes which influence immune cells under pathological conditions.We also describe some of the underlying mechanisms of these changes and their effects.Finally,we describe several studies which use OL-lineage cells as immunotherapeutic targets for demyelination diseases.展开更多
基金supported by grants from the National Institutes of Health(NS094151 and NS105689)the National Multiple Sclerosis Society(RG5239-A-3)(to WL)
文摘The transcription factor nuclear factor κB（NF-κB） plays major roles in inflammatory diseases through regulation of inflammation and cell viability.Multiple sclerosis（MS） is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system（CNS）.It has been shown that NF-κB is activated in multiple cell types in the CNS of MS patients,including T cells,microglia/macrophages,astrocytes,oligodendrocytes,and neurons.Interestingly,data from animal model studies,particularly studies of experimental autoimmune encephalomyelitis,have suggested that NF-κB activation in these individual cell types has distinct effects on the development of MS.In this review,we will cover the current literature on NF-κB and the evidence for its role in the development of MS and its animal model experimental autoimmune encephalomyelitis.
基金supported by the Natural Science Foundation of Zhejiang Province,No.LQ23C090003 (to CZ)the Major Project on Brain Science and Analog Brain Research of Ministry of Science and Technology of China,No.2022ZD0204701 (to MQ)the National Natural Science Foundation of China,No.32170969 (to MQ)。
文摘Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.
基金supported by grants from the National Institutes of Health(NS094151 and NS105689,both to WL)
文摘Activation of the unfolded protein response in response to endoplasmic reticulum stress preserves cell viability and function under stressful conditions.Nevertheless,persistent,unresolvable activation of the unfolded protein response can trigger apoptosis to eliminate stressed cells.Recent studies show that the unfolded protein response plays an important role in the pathogenesis of various disorders of myelin,including multiples sclerosis,Charcot-Marie-Tooth disease,Pelizaeus-Merzbacher disease,vanishing white matter disease,spinal cord injury,tuberous sclerosis complex,and hypoxia-induced perinatal white matter injury.In this review we summarize the current literature on the unfolded protein response and the evidence for its role in the pathogenesis of myelin disorders.
基金supported by the National Natural Science Foundation of China,Nos.82071307(to HL),82271362(to HL),82171294(to JW),82371303(to JW),and 82301460(to PX)the Natural Science Foundation of Jiangsu Province,No.BK20211552(to HL)+1 种基金Suzhou Medical Technology Innovation Project-Clinical Frontier,No.SKY2022002(to ZY)the Science and Education Foundation for Health of Suzhou for Youth,No.KJXW2023001(to XL)。
文摘Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.
基金supported by talent startup funding from Fudan University(Nos.JIF101017,SXF101012,and JIF101047)Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Project(No.2021ZD0201100 Task 4 and No.2021ZD0201104)from the Ministry of Science and Technology(MOST),China+3 种基金Jinsong Wu was supported by Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)ZJ Lab,and operating grant of Shanghai Brain Bank technical system(No.16JC1420103)Edwin Wang was supported by Alberta Innovates Translational Chair Program in Cancer Genomics,the Natural Sciences and Engineering Research Council of Canada(NSERC,No.RGPIN-2017-04885)Canadian Foundation of Innovation(No.36655).
文摘The association of neurogenesis and gliogenesis with glioma remains unclear.By conducting single-cell RNA-seq analyses on 26 gliomas,we reported their classification into primitive oligodendrocyte precursor cell(pri-OPC)-like and radial glia(RG)-like tumors and validated it in a public cohort and TCGA glioma.The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations,and the pri-OPC-like ones were prone to carrying TP53 mutations.Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes,suggesting their distinct immune evasion programs.Furthermore,the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners.Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes.For example,glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes,respectively.Their expression was positively correlated with those of immune checkpoint genes(e.g.,LGALS33)and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells.This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.
基金This work was funded by the Japan Agency for Medical Research and Development(AMED,18ek0109384h0001,I9ek0109384h0002,T.M.,H.Y.,R.T.)Kyoto University MSA Research Fund(RT).S.K.is supported by Grant-in-Aid for Research Activity start-up(18H06088)Grant-in-Aid for Young Scientists(B)(19 K16915)from Japan Society for the Promotion of Science in Japan.
文摘Multiple system atrophy(MSA)is a debilitating and fatal neurodegenerative disorder.The disease severity warrants urgent development of disease-modifying therapy,but the disease pathogenesis is still enigmatic.Neurodegeneration in MSA brains is preceded by the emergence of glial cytoplasmic inclusions(GCIs),which are insoluble α-synuclein accumulations within oligodendrocytes(OLGs).Thus,preventive strategies against GCI formation may suppress disease progression.However,although numerous studies have tried to elucidate the molecular pathogenesis of GCI formation,difficulty remains in understanding the pathological interaction between the two pivotal aspects of GCIs;asynuclein and OLGs.The difficulty originates from several enigmas:1)what triggers the initial generation and possible propagation of pathogenic α-synuclein species?2)what contributes to OLG-specific accumulation of α-synuclein,which is abundantly expressed in neurons but not in OLGs?and 3)how are OLGs and other glial cells affected and contribute to neurodegeneration?The primary pathogenesis of GCIs may involve myelin dysfunaion and dyshomeostasis of the oligodendroglial cellular environment such as autophagy and iron metabolism.We have previously reported that oligodendrocyte precursor cells are more prone to develop intracellular inclusions in the presence of extracellular fibrillary α-synuclein.This finding implies a possibility that the propagation of GCI pathology in MSA brains is mediated through the internalization of pathological α-synuclein into oligodendrocyte precursor cells.In this review,in order to discuss the pathogenesis of GCIs,we will focus on the composition of neuronal and oligodendroglial inclusions in synucleinopathies.Furthermore,we will introduce some hypotheses on how α-synuclein pathology spreads among OLGs in MSA brains,in the light of our data from the experiments with primary oligodendrocyte lineage cell culture.While various reports have focused on the mysterious source of α-synuclein in GCIs,insights into the mecha
基金supported by the National Natural Science Foundation of China,No.81560162the Guangxi Natural Science Foundation of China,No.2018GXNSFAA050052(both YD)。
文摘Methylprednisolone pulse treatment is currently used fo r optic neuritis.It can speed visual recovery,but does not improve the ultimate visual outcomes.Recent studies have repo rted that miR-125 a-5 p has immunomodulatory effects on autoimmune diseases.However,it remains unclear whether miR-125 a-5 p has effects on optic neuritis.In this study,we used adeno-associated virus to overexpress or silence miR-125 a-5 p in mice.We found that silencing miR-125 a-5 p increased the latency of visual evoked potential and aggravated inflammation of the optic nerve.Ove rexpression of miR-125 a-5 p suppressed inflammation of the optic nerve,protected retinal ganglion cells,and increased the percentage of Treg cells.Our findings show that miR-125 a-5 p exhibits anti-inflammatory effects through promoting the diffe rentiation of Treg cells.
基金supported by grants from the National Institutes of Health,No.NS105689(to WL)the Department of Defense through the Multiple Sclerosis Research Program,No.W81XWH-22-1-0757(to WL).
文摘The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.
基金supported by grants from the National Natural Science Foundation of China (32271034,32070964,81971309,32170980,and 32300791)National Key Research and Development Program of China (2021ZD0201703)+4 种基金Chongqing Natural Science Fund for Distinguished Young Scholars (CSTB2023NSCQ-JQX0030)Guangdong Basic and Applied Basic Research Foundation (2022B1515020012,2021A1515110268,2023A1515010651)Shenzhen Medical Research Fund (A2303014)Shenzhen Fundamental Research Program (JCYJ20210324123212035,RCYX20200714114644167,ZDSYS20220606100801003,RCBS20210706092411028,and JCYJ20210324121214039)Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research (ZDSYS20220606100801003).
文摘Oligodendrocyte precursor cells(OPCs)are a heterogeneous multipotent population in the central nervous system(CNS)that appear during embryogenesis and persist as resident cells in the adult brain parenchyma.OPCs could generate oligodendrocytes to participate in myelination.Recent advances have renewed our knowledge of OPC biology by discovering novel markers of oligodendroglial cells,the myelin-independent roles of OPCs,and the regulatory mechanism of OPC development.In this review,we will explore the updated knowledge on OPC identity,their multifaceted roles in the CNS in health and diseases,as well as the regulatory mechanisms that are involved in their developmental stages,which hopefully would contribute to a further understanding of OPCs and attract attention in the field of OPC biology.
基金This work was supported by research grants from Shenzhen Fundamental Research Program(Grants No.RCYX20200714114644167,JCYJ20190809161405495,and JCYJ20210324123212035)National Natural Science Foundation of China(Grants No.81971309,32170980,and 32070964)Guangdong Basic and Applied Basic Research Foundation(Grants No.2019A1515011333 and 2022B1515020012).
文摘Oligodendrocyte lineage cells(OL-lineage cells)are a cell population that are crucial for mammalian central nervous system(CNS)myelination.OL-lineage cells go through developmental stages,initially differentiating into oligodendrocyte precursor cells(OPCs),before becoming immature oligodendrocytes,then mature oligodendrocytes(OLs).While the main function of cell lineage is in myelin formation,and increasing number of studies have turned to explore the immunological characteristics of these cells.Initially,these studies focused on discovering how OPCs and OLs are affected by the immune system,and then,how these immunological changes influence the myelination process.However,recent studies have uncovered another feature of OL-lineage cells in our immune systems.It would appear that OL-lineage cells also express immunological factors such as cytokines and chemokines in response to immune activation,and the expression of these factors changes under various pathologic conditions.Evidence suggests that OL-lineage cells actually modulate immune functions.Indeed,OL-lineage cells appear to play both"victim"and"agent"in the CNS which raises a number of questions.Here,we summarize immunologic changes in OL-lineage cells and their effects,as well as consider OL-lineage cell changes which influence immune cells under pathological conditions.We also describe some of the underlying mechanisms of these changes and their effects.Finally,we describe several studies which use OL-lineage cells as immunotherapeutic targets for demyelination diseases.
