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  1. AU="Palle, Pushpalatha"
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  1. Article ; Online: STAT1 signaling protects self-reactive T cells from control by innate cells during neuroinflammation.

    Arbelaez, Carlos A / Palle, Pushpalatha / Charaix, Jonathan / Bettelli, Estelle

    JCI insight

    2022  Volume 7, Issue 12

    Abstract: The transcription factor STAT1 plays a critical role in modulating the differentiation of CD4+ T cells producing IL-17 and GM-CSF, which promote the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) ...

    Abstract The transcription factor STAT1 plays a critical role in modulating the differentiation of CD4+ T cells producing IL-17 and GM-CSF, which promote the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The protective role of STAT1 in MS and EAE has been largely attributed to its ability to limit pathogenic Th cells and promote Tregs. Using mice with selective deletion of STAT1 in T cells (STAT1CD4-Cre), we identified a potentially novel mechanism by which STAT1 regulates neuroinflammation independently of Foxp3+ Tregs. STAT1-deficient effector T cells became the target of NK cell-mediated killing, limiting their capacity to induce EAE. STAT1-deficient T cells promoted their own killing by producing more IL-2 that, in return, activated NK cells. Elimination of NK cells restored EAE susceptibility in STAT1CD4-Cre mice. Therefore, our study suggests that the STAT1 pathway can be manipulated to limit autoreactive T cells during autoimmunity directed against the CNS.
    MeSH term(s) Animals ; Autoimmunity ; CD4-Positive T-Lymphocytes ; Encephalomyelitis, Autoimmune, Experimental ; Mice ; Multiple Sclerosis ; Neuroinflammatory Diseases ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism
    Chemical Substances STAT1 Transcription Factor ; Stat1 protein, mouse
    Language English
    Publishing date 2022-06-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.148222
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cutting Edge: DOCK8 Regulates a Subset of Dendritic Cells That Is Critical for the Development of Experimental Autoimmune Encephalomyelitis.

    Weliwitigoda, Asanga / Palle, Pushpalatha / Gessner, Melissa / Hubbard, Nicholas W / Oukka, Mohamed / Bettelli, Estelle

    Journal of immunology (Baltimore, Md. : 1950)

    2021  Volume 207, Issue 10, Page(s) 2417–2422

    Abstract: Dedicator of cytokinesis 8 (DOCK8) is a guanine nucleotide exchange factor with an essential role in cytoskeletal rearrangement, cell migration, and survival of various immune cells. Interestingly, DOCK8-deficient mice are resistant to the development of ...

    Abstract Dedicator of cytokinesis 8 (DOCK8) is a guanine nucleotide exchange factor with an essential role in cytoskeletal rearrangement, cell migration, and survival of various immune cells. Interestingly, DOCK8-deficient mice are resistant to the development of experimental autoimmune encephalomyelitis (EAE). To understand if EAE resistance in these mice results from an alteration in dendritic cell (DC) functions, we generated mice with conditional deletion of DOCK8 in DCs and observed attenuated EAE in these mice compared with control mice. Additionally, we demonstrated that DOCK8 is important for the existence of splenic conventional DC2 and lymph node migratory DCs and further established that migratory DC, rather than resident DC, are essential for the generation and proliferation of pathogenic T cell populations upon immunization with myelin Ag in adjuvant. Therefore, our data suggest that limiting migratory DCs through DOCK8 deletion and possibly other mechanisms could limit the development of CNS autoimmunity.
    MeSH term(s) Animals ; Dendritic Cells/immunology ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Female ; Guanine Nucleotide Exchange Factors/immunology ; Male ; Mice ; Mice, Inbred C57BL
    Chemical Substances Dock8 protein, mouse ; Guanine Nucleotide Exchange Factors
    Language English
    Publishing date 2021-10-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2001294
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Bone marrow chimeras-a vital tool in basic and translational research.

    Ferreira, Filipa M / Palle, Pushpalatha / Vom Berg, Johannes / Prajwal, Prajwal / Laman, Jon D / Buch, Thorsten

    Journal of molecular medicine (Berlin, Germany)

    2019  Volume 97, Issue 7, Page(s) 889–896

    Abstract: Bone marrow chimeras are used routinely in immunology research as well as in other fields of biology. Here, we provide a concise state-of-the-art review about the types of chimerisms that can be achieved and the type of information that each model ... ...

    Abstract Bone marrow chimeras are used routinely in immunology research as well as in other fields of biology. Here, we provide a concise state-of-the-art review about the types of chimerisms that can be achieved and the type of information that each model generates. We include separate sections for caveats and future developments. We provide examples from the literature in which different types of chimerism were employed to answer specific questions. While simple bone marrow chimeras allow to dissect the role of genes in distinct cell populations such as the hematopoietic cells versus non-hematopoietic cells, mixed bone marrow chimeras can provide detailed information about hematopoietic cell types and the intrinsic and extrinsic roles of individual genes. The advantages and caveats of bone marrow chimerism for the study of microglia are addressed, as well as alternatives to irradiation that minimize blood-brain-barrier disruption. Elementary principles are introduced and their potential is exemplified through summarizing recent studies.
    MeSH term(s) Animals ; Bone Marrow/metabolism ; Chimera/metabolism ; Hematopoietic Stem Cells/metabolism ; Immune Reconstitution ; Myeloid Cells/metabolism ; Translational Research, Biomedical
    Language English
    Publishing date 2019-04-26
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1223802-8
    ISSN 1432-1440 ; 0946-2716
    ISSN (online) 1432-1440
    ISSN 0946-2716
    DOI 10.1007/s00109-019-01783-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cytokine Signaling in Multiple Sclerosis and Its Therapeutic Applications.

    Palle, Pushpalatha / Monaghan, Kelly L / Milne, Sarah M / Wan, Edwin C K

    Medical sciences (Basel, Switzerland)

    2017  Volume 5, Issue 4

    Abstract: Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known but it is widely accepted that it is autoimmune in nature. Disease onset is believed to be initiated by the activation of CD4+ T ... ...

    Abstract Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known but it is widely accepted that it is autoimmune in nature. Disease onset is believed to be initiated by the activation of CD4+ T cells that target autoantigens of the central nervous system (CNS) and their infiltration into the CNS, followed by the expansion of local and infiltrated peripheral effector myeloid cells that create an inflammatory milieu within the CNS, which ultimately lead to tissue damage and demyelination. Clinical studies have shown that progression of MS correlates with the abnormal expression of certain cytokines. The use of experimental autoimmune encephalomyelitis (EAE) model further delineates the role of these cytokines in neuroinflammation and the therapeutic potential of manipulating their biological activity in vivo. In this review, we will first present an overview on cytokines that may contribute to the pathogenesis of MS or EAE, and provide successful examples and roadblock of translating data obtained from EAE to MS. We will then focus in depth on recent findings that demonstrate the pathological role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in MS and EAE, and briefly discuss the potential of targeting effector myeloid cells as a treatment strategy for MS.
    Language English
    Publishing date 2017-10-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2754473-4
    ISSN 2076-3271 ; 2076-3271
    ISSN (online) 2076-3271
    ISSN 2076-3271
    DOI 10.3390/medsci5040023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The more the merrier? Scoring, statistics and animal welfare in experimental autoimmune encephalomyelitis.

    Palle, Pushpalatha / Ferreira, Filipa M / Methner, Axel / Buch, Thorsten

    Laboratory animals

    2016  Volume 50, Issue 6, Page(s) 427–432

    Abstract: Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune ... ...

    Abstract Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants. Varying scales with differing parameters are used and thus limit comparability of experiments. Incorrect use of statistical analysis tools to assess EAE data is commonplace. In experimental practice the clinical score is used not only as an experimental readout, but also as a parameter to determine animal welfare actions. Often overlooked factors such as the animal's ability to sense its compromised motoric abilities, drastic though transient weight loss, and also the possibility of neuropathic pain, make the assessment of severity a difficult task and pose a problem for experimental refinement.
    Language English
    Publishing date 2016-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 391008-8
    ISSN 1758-1117 ; 0023-6772
    ISSN (online) 1758-1117
    ISSN 0023-6772
    DOI 10.1177/0023677216675008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The more the merrier? Scoring, statistics and animal welfare in experimental autoimmune encephalomyelitis

    Palle, Pushpalatha / Buch, Thorsten / Ferreira, Filipa M / Golledge, H / Jirkof, P / Methner, Axel

    Laboratory animals. 2016 Dec., v. 50, no. 6

    2016  

    Abstract: Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune ... ...

    Abstract Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants. Varying scales with differing parameters are used and thus limit comparability of experiments. Incorrect use of statistical analysis tools to assess EAE data is commonplace. In experimental practice the clinical score is used not only as an experimental readout, but also as a parameter to determine animal welfare actions. Often overlooked factors such as the animal’s ability to sense its compromised motoric abilities, drastic though transient weight loss, and also the possibility of neuropathic pain, make the assessment of severity a difficult task and pose a problem for experimental refinement.
    Keywords animal models ; animal welfare ; autoimmune diseases ; central nervous system ; disease course ; drugs ; encephalitis ; humans ; laboratory animals ; pain ; sclerosis ; statistical analysis ; transgenes ; weight loss
    Language English
    Dates of publication 2016-12
    Size p. 427-432.
    Publishing place SAGE Publications
    Document type Article
    ZDB-ID 391008-8
    ISSN 1758-1117 ; 0023-6772
    ISSN (online) 1758-1117
    ISSN 0023-6772
    DOI 10.1177/0023677216675008
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Mature oligodendrocytes actively increase in vivo cytoskeletal plasticity following CNS damage.

    Locatelli, Giuseppe / Baggiolini, Arianna / Schreiner, Bettina / Palle, Pushpalatha / Waisman, Ari / Becher, Burkhard / Buch, Thorsten

    Journal of neuroinflammation

    2015  Volume 12, Page(s) 62

    Abstract: Background: Oligodendrocytes are myelinating cells of the central nervous system which support functionally, structurally, and metabolically neurons. Mature oligodendrocytes are generally believed to be mere targets of destruction in the context of ... ...

    Abstract Background: Oligodendrocytes are myelinating cells of the central nervous system which support functionally, structurally, and metabolically neurons. Mature oligodendrocytes are generally believed to be mere targets of destruction in the context of neuroinflammation and tissue damage, but their real degree of in vivo plasticity has become a matter of debate. We thus investigated the in vivo dynamic, actin-related response of these cells under different kinds of demyelinating stress.
    Methods: We used a novel mouse model (oLucR) expressing luciferase in myelin oligodendrocyte glycoprotein-positive oligodendrocytes under the control of a β-actin promoter. Activity of this promoter served as surrogate for dynamics of the cytoskeleton gene transcription through recording of in vivo bioluminescence following diphtheria toxin-induced oligodendrocyte death and autoimmune demyelination. Cytoskeletal gene expression was quantified from mature oligodendrocytes directly isolated from transgenic animals through cell sorting.
    Results: Experimental demyelinating setups augmented oligodendrocyte-specific in vivo bioluminescence. These changes in luciferase signal were confirmed by further ex vivo analysis of the central nervous system tissue from oLucR mice. Increase in bioluminescence upon autoimmune inflammation was parallel to an oligodendrocyte-specific increased transcription of β-tubulin.
    Conclusions: Mature oligodendrocytes acutely increase their cytoskeletal plasticity in vivo during demyelination. They are therefore not passive players under demyelinating conditions but can rather react dynamically to external insults.
    MeSH term(s) Animals ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/metabolism ; Central Nervous System/metabolism ; Central Nervous System Diseases/pathology ; Cytokines/metabolism ; Cytoskeleton/metabolism ; Diphtheria Toxin/pharmacology ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/chemically induced ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Gene Expression Regulation/genetics ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; In Vitro Techniques ; Mice ; Mice, Transgenic ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Myelin-Oligodendrocyte Glycoprotein/genetics ; Myelin-Oligodendrocyte Glycoprotein/metabolism ; Oligodendroglia/metabolism
    Chemical Substances Aif1 protein, mouse ; Calcium-Binding Proteins ; Cytokines ; Diphtheria Toxin ; Microfilament Proteins ; Myelin-Oligodendrocyte Glycoprotein ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2015-04-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1742-2094
    ISSN (online) 1742-2094
    DOI 10.1186/s12974-015-0271-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Online ; Thesis: Triggers of anti-CNS autoimmunity in the mouse model of Multiple Sclerosis

    Palle, Pushpalatha Verfasser] / [Costa, Clarissa Prazeres da [Akademischer Betreuer] / Costa, Clarissa Prazeres da [Gutachter] / Klingenspor, Martin [Gutachter]

    2017  

    Author's details Pushpalatha Palle ; Gutachter: Clarissa Prazeres da Costa, Martin Klingenspor ; Betreuer: Clarissa Prazeres da Costa
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Universitätsbibliothek der TU München
    Publishing place München
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  9. Article ; Online: T cell-specific inactivation of mouse CD2 by CRISPR/Cas9.

    Beil-Wagner, Jane / Dössinger, Georg / Schober, Kilian / vom Berg, Johannes / Tresch, Achim / Grandl, Martina / Palle, Pushpalatha / Mair, Florian / Gerhard, Markus / Becher, Burkhard / Busch, Dirk H / Buch, Thorsten

    Scientific reports

    2016  Volume 6, Page(s) 21377

    Abstract: The CRISPR/Cas9 system can be used to mutate target sequences by introduction of double-strand breaks followed by imprecise repair. To test its use for conditional gene editing we generated mice transgenic for CD4 promoter-driven Cas9 combined with guide ...

    Abstract The CRISPR/Cas9 system can be used to mutate target sequences by introduction of double-strand breaks followed by imprecise repair. To test its use for conditional gene editing we generated mice transgenic for CD4 promoter-driven Cas9 combined with guide RNA targeting CD2. We found that within CD4(+) and CD8(+) lymphocytes from lymph nodes and spleen 1% and 0.6% were not expressing CD2, respectively. T cells lacking CD2 carryied mutations, which confirmed that Cas9 driven by cell-type specific promoters can edit genes in the mouse and may thus allow targeted studies of gene function in vivo.
    MeSH term(s) Animals ; Base Sequence ; CD2 Antigens/genetics ; CD2 Antigens/immunology ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CRISPR-Cas Systems ; Gene Editing/methods ; Gene Silencing ; Genetic Engineering ; Genetic Vectors/chemistry ; Genetic Vectors/metabolism ; Immunophenotyping ; Lymph Nodes/cytology ; Lymph Nodes/immunology ; Mice ; Mice, Transgenic ; Mutation ; Promoter Regions, Genetic ; RNA, Guide, CRISPR-Cas Systems/genetics ; RNA, Guide, CRISPR-Cas Systems/metabolism ; Spleen/cytology ; Spleen/immunology
    Chemical Substances CD2 Antigens ; RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2016-02-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep21377
    Database MEDical Literature Analysis and Retrieval System OnLINE

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