surgical-transplantation-mouse-neural-stem-cells-into-spinal-cords

Surgical Transplantation of Mouse Neural Stem Cells into the Spinal Cords of Mice Infected with Neurotropic Mouse Hepatitis Virus

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV) develop pathological and clinical outcomes similar to patients with the ...

two-photon-imaging-of-cellular-dynamics-in-the-mouse-spinal-cord

Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord

Two-photon (2P) microscopy is utilized to reveal cellular dynamics and interactions deep within living, intact tissues. Here, we present a method for ...

A signaling role for T cell leukemia-1 (TCL1) during T cell development or in premalignant T cell expansions and mature T cell tumors is unknown. In this study, TCL1 is shown to regulate the growth and survival of peripheral T cells but not precursor thymocytes. Proliferation is increased by TCL1-induced lowering of the TCR threshold for CD4(+) and CD8(+) T cell activation through both PI3K-Akt and protein kinase C-MAPK-ERK signaling pathways. This effect is submaximal as CD28 costimulation coupled to TCL1 expression additively accelerates dose-dependent T cell growth. In addition to its role in T cell proliferation, TCL1 also increases IFN-gamma levels from Th1-differentiated T cells, an effect that may provide a survival advantage during premalignant T cell expansions and in clonal T cell tumors. Combined, these data indicate a role for TCL1 control of growth and effector T cell functions, paralleling features provided by TCR-CD28 costimulation. These results also provide a more detailed mechanism for TCL1-augmented signaling and help explain the delayed occurrence of mature T cell expansions and leukemias despite tumorigenic TCL1 dysregulation that begins in early thymocytes.

T cell leukemia-1 modulates TCR signal strength and IFN-gamma levels through phosphatidylinositol 3-kinase and protein kinase C pathway activation.

T-Zell-Leuk&#xE4;mie-1 moduliert TCR Signalst&#xE4;rke und IFN-gamma Ebenen durch Phosphatidylinositol 3-Kinase und Proteinkinase C-Signalweg-Aktivierung.

Despite altered regulation of insulin signaling, Pten(+/-) heterodeficient standard diet-fed mice, approximately 4 months old, exhibit normal fasting glucose and insulin levels. We report here a stable isotope flux phenotyping study of this "silent" phenotype, in which tissue-specific insulin effects in whole-body Pten(+/-)-deficient mice were dissected in vivo. Flux phenotyping showed gain of function in Pten(+/-) mice, seen as increased peripheral glucose disposal, and compensation by a metabolic feedback mechanism that 1) decreases hepatic glucose recycling via suppression of glucokinase expression in the basal state to preserve hepatic glucose production and 2) increases hepatic responsiveness in the fasted-to-fed transition. In Pten(+/-) mice, hepatic gene expression of glucokinase was 10-fold less than wild-type (Pten(+/+)) mice in the fasted state and reached Pten(+/+) values in the fed state. Glucose-6-phosphatase expression was the same for Pten(+/-) and Pten(+/+) mice in the fasted state, and its expression for Pten(+/-) was 25% of Pten(+/+) in the fed state. This study demonstrates how intra- and interorgan flux compensations can preserve glucose homeostasis (despite a specific gene defect that accelerates glucose disposal) and how flux phenotyping can dissect these tissue-specific flux compensations in mice presenting with a "silent" phenotype.

Decreased hepatic futile cycling compensates for increased glucose disposal in the Pten heterodeficient mouse.

Trotz der ge&auml;nderten Verordnung von Insulin Signalling, Pten(+/-) Heterodeficient Norm Di&auml;t gef&uuml;tterten M&auml;use, weisen Sie ca. 4 Monate alt, normaler N&uuml;chtern-Glukose und Insulinspiegel. Wir berichten hier eine stabiles Isotop Flussmittel pathologies Studie &uuml;ber diese &quot;Stille&quot; Ph&auml;notyp, in welche Gewebe-spezifischen Insulin-Effekte im ganzen K&ouml;rper Pten (+/-)-unzul&auml;ngliche M&auml;usen wurden in-vivo seziert. Flussmittel pathologies zeigte gewinnen Funktion in Pten(+/-) M&auml;use, gesehen, wie erh&ouml;hte periphere Glukose-Entsorgung und Entsch&auml;digung durch eine metabolische Feedback-Mechanismus, der 1) verringert hepatische Glukose Verwertung &uuml;ber Unterdr&uuml;ckung der Glucokinase Ausdruck in den basalen Zustand, hepatische Glukose-Produktion zu bewahren und 2) erh&ouml;ht Leber Reaktionsf&auml;higkeit beim &Uuml;bergang fastete an verf&uuml;ttert. Bei Pten(+/-) M&auml;usen hepatische Genexpression von Glucokinase war 10-fache weniger als Wildtyp (Pten(+/+)) M&auml;use in der schnellste Staat und Pten(+/+) Werte in den gef&uuml;ttert Zustand erreicht. Glukose-6-Phosphatase-Ausdruck war f&uuml;r Pten(+/-) und Pten(+/+) M&auml;use in der schnellste Staat und seinen Ausdruck f&uuml;r Pten(+/-) 25 % des Pten(+/+) im Zustand gef&uuml;ttert. Diese Studie zeigt wie Intra- und interorgan Flussmittel Entsch&auml;digungen Glukose Hom&ouml;ostase (trotz einer bestimmten Gen-defekt, der Glukose-Entsorgung beschleunigt) erhalten und wie Flussmittel pathologies diese Gewebe-spezifischen Flussmittel-Entsch&auml;digungen bei M&auml;usen mit einem &quot;stillen&quot; Ph&auml;notyp zerlegen kann k&ouml;nnen.

Erh&ouml;hte Glukose-Entsorgung in der Pten Heterodeficient Maus gleicht verminderte hepatische vergeblichen Radfahren.

Axl is a receptor tyrosine kinase implicated in cell survival following growth factor withdrawal and other stressors. The binding of Axl's ligand, growth arrest-specific protein 6 (Gas6), results in Axl autophosphorylation, recruitment of signaling molecules, and activation of downstream survival pathways. Pull-down assays and immunoprecipitations using wildtype and mutant Axl transfected cells determined that Axl directly binds growth factor receptor-bound protein 2 (Grb2) at pYVN and the p85 subunit of phosphatidylinositol-3 kinase (PI3 kinase) at two pYXXM sites (pY779 and pY821). Also, p85 can indirectly bind to Axl via an interaction between p85's second proline-rich region and the N-terminal SH3 domain of Grb2. Further, Grb2 and p85 can compete for binding at the pY821VNM site. Gas6-stimulation of Axl-transfected COS7 cells recruited activated PI3 kinase and phosphorylated Akt. An interaction between Axl, p85 and Grb2 was confirmed in brain homogenates, enriched populations of O4+ oligodendrocytes, and O4- flow-through prepared from day 10 mouse brain, indicating that cells with active Gas6/Axl signal through Grb2 and the PI3 kinase/Akt pathways.

In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation.

Axl ist ein Rezeptor-Tyrosinkinase Zelle &Uuml;berleben in Verbindung gebracht nach Wachstumsfaktor-R&uuml;ckzug und anderen Stressoren. Die Bindung von Axl Ligand, Wachstum Verhaftung-spezifische Protein 6 (Gas6), f&uuml;hrt zu Axl Autophosphorylierung, Rekrutierung von signalisierende Molek&uuml;le und Aktivierung der nachgeschalteten &uuml;berleben Bahnen. Pulldown-Assays und Immunpr&auml;zipitation mit Wildtyp und Mutanten Axl transfected Zellen ermittelt, dass Axl direkt Wachstumsfaktor-Rezeptor gebundene Protein 2 (Grb2) bei pYVN und der p85-Untereinheit der Phosphatidylinositol-3-Kinase (PI3-Kinase) an zwei pYXXM Standorten (pY779 und pY821) bindet. Dar&uuml;ber hinaus k&ouml;nnen p85 indirekt &uuml;ber eine Interaktion zwischen p85 des zweiten Prolin-reiche Region und der N-terminalen SH3-Dom&auml;ne des Grb2 an Axl binden. Dar&uuml;ber hinaus k&ouml;nnen Grb2 und p85 f&uuml;r die Bindung am Standort pY821VNM konkurrieren. Gas6-Stimulation COS7 Axl-transfected Zellen rekrutiert PI3-Kinase aktiviert und phosphoryliert Akt. Eine Interaktion zwischen Axl, p85 und Grb2 im Gehirn Homogenates, angereicherten Populationen von O4 + Oligodendrozyten, best&auml;tigt wurde, und O4-Passagen-vorbereitet von Tag 10 Maus Gehirn, darauf hinweist, dass Zellen mit aktiven Gas6/Axl durch Grb2 und die PI3-Kinase/Akt-Wege zu signalisieren.

Im Gehirn Rekruten Axl Grb2 und der p85 regulatorische Untereinheit der PI3-Kinase; in-vitro-Mutagenese definiert die erforderlichen Bindungsstellen f&uuml;r nachgeschaltete Akt-Aktivierung.

Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer ( approximately 150 kd), and soluble Axl (80 kd) were all significantly elevated in homogenates from established multiple sclerosis lesions comprised of both chronic active and chronic silent lesions. Whereas in normal tissue Gas6 positively correlated with soluble Axl and Mer, there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin, proteins that are associated with Axl and Mer solubilization. Soluble Axl and Mer are both known to act as decoy receptors and block Gas6 binding to membrane-bound receptors. These data suggest that in multiple sclerosis lesions, dysregulation of protective Gas6 receptor signaling may prolong lesion activity.

Up-regulation of soluble Axl and Mer receptor tyrosine kinases negatively correlates with Gas6 in established multiple sclerosis lesions.

Multiple Sklerose ist eine Erkrankung, die durch Entz&uuml;ndungen, Demyelinisierung und axonale Sch&auml;den gekennzeichnet ist; Sie bildet letztlich Gliotic Narben und L&auml;sionen, die erheblich die Funktion des zentralen Nervensystems beeintr&auml;chtigen. Beweise zufolge zuvor ge&auml;nderte Wachstumsfaktor Rezeptor Signalgebung L&auml;sion Gr&uuml;ndung tr&auml;gt behindert die Genesung, und spielt eine Rolle im Krankheitsverlauf. Wachstum Verhaftung-spezifische Protein 6 (Gas6), den Liganden f&uuml;r die TAM-Rezeptor-Tyrosin Kinase Familie, bestehend aus Tyro3, Axl und Mer, ist wichtig f&uuml;r Zellwachstum, &Uuml;berleben und Abfertigung der Tr&uuml;mmer. In dieser Studie zeigen wir, dass Ebenen membrangebundener Mer (205 kd), l&ouml;sliche Mer (ca. 150 kd), und l&ouml;slichen Axl (80 kd) wurden alle deutlich in Homogenates aus etablierten Multiple-Sklerose-L&auml;sionen umfasste sowohl chronische aktive und chronische Stille L&auml;sionen erhoben. W&auml;hrend in normalem Gewebe Gas6 positiv mit l&ouml;slichen Axl und Mer wurde, gab es eine negative Korrelation zwischen Gas6 und l&ouml;slichen Axl und Mer in etablierten Multiple-Sklerose-L&auml;sionen. Dar&uuml;ber hinaus wurden angestiegener l&ouml;sliche Axl und Mer mit h&ouml;heres Ma&szlig; an Reife ADAM17, Reife ADAM10 und Furin, Proteine, die mit Axl und Mer Solubilization verbunden sind. L&ouml;sliche Axl und Mer sind beide bekannt als K&ouml;der-Rezeptoren und Gas6 Bindung an Membrane-springen-Rezeptoren zu blockieren. Diese Daten legen nahe, dass bei multipler Sklerose Hautver&auml;nderungen, Dysregulation der sch&uuml;tzende Gas6 Rezeptor Signalisierung L&auml;sion Aktivit&auml;t verl&auml;ngern kann.

Bis-Regelung der l&ouml;slichen Axl und Mer-Rezeptor-Tyrosin-Kinasen korreliert negativ mit Gas6 in etablierten Multiple-Sklerose-L&auml;sionen.

Axl, zusammen mit Tyro3 und Mer, bilden die TAM-Familie von Rezeptor Tyrosinkinasen. Im Nervensystem werden auf mehrere Zelltypen Axl und seine Ligand Wachstum-Festnahme-spezifische Protein 6 (Gas6) ausgedr&uuml;ckt. Axl-Funktionen in der D&auml;mpfung der Immunantwort, Zelle regulieren Zytokin-Sekretion, clearing Apoptotic Zellen und Schutt und warten &uuml;berleben. Axl ist herraufreguliert in den verschiedenen Krankheitzust&auml;nden, z. B. in der Cuprizone induziert durch Toxizit&auml;t Modell der Demyelinisierung und Multiple Sklerose (MS) L&auml;sionen, darauf hindeutet, dass er eine Rolle in der Pathogenese der Krankheit spielt. Um dies zu testen, studierte wir die Empf&auml;nglichkeit von Axl-/-M&auml;use zu experimentellen autoimmunen Enzephalomyelitis (EAE), einem Tiermodell f&uuml;r Multiple Sklerose.

Verlust der Rezeptor-Tyrosinkinase Axl f&uuml;hrt zu verst&auml;rkten Entz&uuml;ndung im ZNS und Entfernung von Myelin Tr&uuml;mmer w&auml;hrend der experimentellen autoimmunen Enzephalomyelitis verz&ouml;gert.

Axl, together with Tyro3 and Mer, constitute the TAM family of receptor tyrosine kinases. In the nervous system, Axl and its ligand Growth-arrest-specific protein 6 (Gas6) are expressed on multiple cell types. Axl functions in dampening the immune response, regulating cytokine secretion, clearing apoptotic cells and debris, and maintaining cell survival. Axl is upregulated in various disease states, such as in the cuprizone toxicity-induced model of demyelination and in multiple sclerosis (MS) lesions, suggesting that it plays a role in disease pathogenesis. To test for this, we studied the susceptibility of Axl-/- mice to experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis.

Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during experimental autoimmune encephalomyelitis.

The abundant axonal microtubule-associated protein tau regulates microtubule and actin dynamics, thereby contributing to normal neuronal function. We examined whether mice deficient in tau (Tau(-/-)) or with high levels of human tau differ from wild-type (WT) mice in their susceptibility to neuroaxonal injury in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. After sensitization with MOG35-55, there was no difference in clinical disease course between human tau and WT mice, but Tau mice had more severe clinical disease and significantly more axonal damage in spinal cord white matter than those in WT mice. Axonal damage in gray matter correlated with clinical severity in individual mice. By immunoblot analysis, the early microtubule-associated protein-1b was increased 2-fold in the spinal cords of Tau mice with chronic experimental autoimmune encephalomyelitis versus naive Tau mice. This difference was not detected in comparable WT animals, which suggests that there was compensation for the loss of tau in the deficient mice. In addition, levels of the growth arrest-specific protein 7b, a tau-binding protein that is stabilized when bound to tau, were higher in WT than those in Tau(-/-) spinal cord samples. These data indicate that loss of tau exacerbates experimental autoimmune encephalomyelitis and suggest that maintaining tau integrity might reduce the axonal damage that occurs in inflammatory neurodegenerative diseases such as multiple sclerosis.

Mice devoid of Tau have increased susceptibility to neuronal damage in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.

Transplantation of syngeneic neural progenitor cells (NPCs) into mice persistently infected with the JHM strain of mouse hepatitis virus (JHMV) results in enhanced differentiation into oligodendrocyte progenitor cells that is associated with remyelination, axonal sparing, and clinical improvement. Whether allogeneic NPCs are tolerated or induce immune-mediated rejection is controversial and poorly defined under neuroinflammatory demyelinating conditions. We have used the JHMV-induced demyelination model to evaluate the antigenicity of transplanted allogeneic NPCs within the central nervous system (CNS) of mice with established immune-mediated demyelination. Cultured NPCs constitutively expressed the costimulatory molecules CD80/CD86, and IFN-γ treatment induced expression of MHC class I and II antigens. Injection of allogeneic C57BL/6 NPCs (H-2b background) led to a delayed type hypersensitivity response in BALB/c (H-2d background) mice associated with T-cell proliferation and IFN-γ secretion following coculture with allogeneic NPCs. Transplantation of MHC-mismatched NPCs into JHMV-infected mice resulted in increased transcripts encoding the T-cell chemoattractant chemokines CXCL9 and CXCL10 that correlated with increased T-cell infiltration that was associated with NPC rejection. Treatment of MHC-mismatched mice with T-cell subset-specific depleting antibodies increased survival of allogeneic NPCs without affecting commitment to an oligodendrocyte lineage. Collectively, these results show that allogeneic NPCs are antigenic, and T-cells contribute to rejection following transplantation into an inflamed CNS suggesting that immunomodulatory treatments may be necessary to prolong survival of allogeneic cells.

MHC mismatch results in neural progenitor cell rejection following spinal cord transplantation in a model of viral-induced demyelination.

Inoculation with the neurotropic JHM strain of mouse hepatitis virus (MHV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis in which virus preferentially replicates within glial cells while excluding neurons. Control of viral replication during acute disease is mediated by infiltrating virus-specific T cells via cytokine secretion and cytolytic activity, however sterile immunity is not achieved and virus persists resulting in chronic neuroinflammation associated with demyelination. CXCR2 is a chemokine receptor that upon binding to specific ligands promotes host defense through recruitment of myeloid cells to the CNS as well as protecting oligodendroglia from cytokine-mediated death in response to MHV infection. These findings highlight growing evidence of the diverse and important role of CXCR2 in regulating neuroinflammatory diseases.

The chemokine receptor CXCR2 and coronavirus-induced neurologic disease.

AKT3, a member of the serine/threonine kinase AKT family, is involved in a variety of biologic processes. AKT3 is expressed in immune cells and is the major AKT isoform in the CNS representing 30% of the total AKT expressed in spinal cord, and 50% in the brain. Myelin-oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model in which lymphocytes and monocytes enter the CNS, resulting in inflammation, demyelination, and axonal injury. We hypothesized that during EAE, deletion of AKT3 would negatively affect the CNS of AKT3(-/-) mice, making them more susceptible to CNS damage. During acute EAE, AKT3(-/-)mice were more severely affected than wild type (WT) mice. Evaluation of spinal cords showed that during acute and chronic disease, AKT3(-/-) spinal cords had more demyelination compared with WT spinal cords. Quantitative RT-PCR determined higher levels of IL-2, IL-17, and IFN-γ mRNA in spinal cords from AKT3(-/-) mice than WT. Experiments using bone marrow chimeras demonstrated that AKT3(-/-) mice receiving AKT3-deficient bone marrow cells had elevated clinical scores relative to control WT mice reconstituted with WT cells, indicating that altered function of both CNS cells and bone marrow-derived immune cells contributed to the phenotype. Immunohistochemical analysis revealed decreased numbers of Foxp3(+) regulatory T cells in the spinal cord of AKT3(-/-) mice compared with WT mice, whereas in vitro suppression assays showed that AKT3-deficient Th cells were less susceptible to regulatory T cell-mediated suppression than their WT counterparts. These results indicate that AKT3 signaling contributes to the protection of mice against EAE.

Suppression of inflammatory responses during myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis is regulated by AKT3 signaling.

Neural precursor cells (NPCs) are the subject of intense investigation for their potential to treat neurodegenerative disorders, yet the consequences of neuroinvasive virus infection of NPCs remain unclear. This study demonstrates that NPCs support replication following infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV). JHMV infection leads to increased cell death and dampens IFN-γ-induced MHC class II expression. Importantly, cytokines secreted by CD4+ T cells inhibit JHMV replication in NPCs, and CD8+ T cells specifically target viral peptide-pulsed NPCs for lysis. Furthermore, treatment with IFN-γ inhibits JHMV replication in a dose-dependent manner. Together, these findings suggest that T cells play a critical role in controlling replication of a neurotropic virus in NPCs, a finding which has important implications when considering immune modulation for NPC-based therapies for treatment of human neurologic diseases.

T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells.

This unit describes the preparation and transplantation of human neural precursor cells (hNPCs) and mouse neural precursor cells (mNPCs) into the thoracic region of the mouse spinal cord. The techniques in this unit also describe how to prepare the mouse for surgery by performing a laminectomy to expose the spinal cord for transplantation. NPCs genetically labeled with eGFP transplanted into the spinal cord of a mouse following viral-mediated demyelination can efficiently be detected via eGFP expression. Transplantation of these cells into the spinal cord is an efficacious way to determine their effects in neurological disorders such as multiple sclerosis, Alzheimer's disease, and spinal cord injury.

Intraspinal transplantation of mouse and human neural precursor cells.

Neural precursor cells (NPCs) offer a promising approach for treating demyelinating diseases. However, the cellular dynamics that underlie transplanted NPC-mediated remyelination have not been described. Using two-photon imaging of a newly developed ventral spinal cord preparation and a viral model of demyelination, we describe the motility and intercellular interactions of transplanted mouse NPCs expressing green fluorescent protein (GFP) with damaged axons expressing yellow fluorescent protein (YFP). Our findings reveal focal axonal degeneration that occurs in the ventral side of the spinal cord within 1 wk following intracranial instillation with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Axonal damage precedes extensive demyelination and is characterized by swelling along the length of the axon, loss of YFP signal, and transected appearance. NPCs engrafted into spinal cords of JHMV-infected mice exhibited diminished migration velocities and increased proliferation compared with transplanted cells in noninfected mice. NPCs preferentially accumulated within areas of axonal damage, initiated direct contact with axons, and subsequently expressed the myelin proteolipid protein gene, initiating remyelination. These findings indicate that NPCs transplanted into an inflammatory demyelinating microenvironment participate directly in therapeutic outcome through the wrapping of myelin around damaged neurons.

Two-photon imaging of remyelination of spinal cord axons by engrafted neural precursor cells in a viral model of multiple sclerosis.

Transplantation of major histocompatibility complex-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing-activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2(b) ) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d) ) mice resulted in infiltration of NKG2D(+) CD49b(+) NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Furthermore, transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D/RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway.

ArticleTotal : 2	Year
Publication title Cited by 14	2011
Publication title Cited by 5	2015

Article	Year
T cell leukemia-1 modulates TCR signal strength and IFN-gamma levels through phosphatidylinositol 3-kinase and protein kinase C pathway activation. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 16002684	2005
Decreased hepatic futile cycling compensates for increased glucose disposal in the Pten heterodeficient mouse. Diabetes\| PubMed ID: 17130482	2006
In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation. Journal of neurochemistry\| PubMed ID: 18346204	2008
Up-regulation of soluble Axl and Mer receptor tyrosine kinases negatively correlates with Gas6 in established multiple sclerosis lesions. The American journal of pathology\| PubMed ID: 19541935	2009
Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during experimental autoimmune encephalomyelitis. Journal of neuroinflammation\| PubMed ID: 21569627	2011
Mice devoid of Tau have increased susceptibility to neuronal damage in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Journal of neuropathology and experimental neurology\| PubMed ID: 22487860	2012
MHC mismatch results in neural progenitor cell rejection following spinal cord transplantation in a model of viral-induced demyelination. Stem cells (Dayton, Ohio)\| PubMed ID: 22969049	2012
The chemokine receptor CXCR2 and coronavirus-induced neurologic disease. Virology\| PubMed ID: 23217621	2013
Suppression of inflammatory responses during myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis is regulated by AKT3 signaling. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 23335751	2013
T cell mediated suppression of neurotropic coronavirus replication in neural precursor cells. Virology\| PubMed ID: 24418558	2014
Intraspinal transplantation of mouse and human neural precursor cells. Current protocols in stem cell biology\| PubMed ID: 24510791	2013
Two-photon imaging of remyelination of spinal cord axons by engrafted neural precursor cells in a viral model of multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 24843159	2014
Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis. Stem cells (Dayton, Ohio)\| PubMed ID: 24898518	2014

Jason G. Weinger

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