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  1. AU="Tesfagiorgis, Yodit"
  2. AU="Abokyi, Samuel" AU="Abokyi, Samuel"
  3. AU="Levy, Sharon" AU="Levy, Sharon"
  4. AU="Sanchez-Vizuete, P"
  5. AU="Akcay, S"
  6. AU="Paul, S Yu"
  7. AU="Lin, Ching-Hao"
  8. AU="Pathare, Varsha S"
  9. AU="Holden, Shelley L"
  10. AU="Cho, Sungkyu"
  11. AU="Gao, Xiya"
  12. AU="Hou, Jiazi"
  13. AU="Mallik, P."

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  1. Artikel ; Online: Systemic administration of anti-CD20 indirectly reduces B cells in the inflamed meninges in a chronic model of central nervous system autoimmunity.

    Tesfagiorgis, Yodit / Kemal, Eden A / Craig, Heather C / Parham, Kate A / Kerfoot, Steven M

    Journal of neuroimmunology

    2023  Band 387, Seite(n) 578267

    Abstract: Anti-CD20 B cell depleting therapies have demonstrated that B cells are important drivers of disease progress in Multiple Sclerosis, although the pathogenic mechanisms are not well understood. A population of B cells accumulates in the inflamed meninges ... ...

    Abstract Anti-CD20 B cell depleting therapies have demonstrated that B cells are important drivers of disease progress in Multiple Sclerosis, although the pathogenic mechanisms are not well understood. A population of B cells accumulates in the inflamed meninges in MS and also some chronic animal models of disease, typically adjacent to demyelinating lesions. The role of these meningeal B cells in disease is not known, nor is their susceptibility to anti-CD20 therapy. Here, we administered anti-CD20 to 2D2 IgH
    Mesh-Begriff(e) Mice ; Animals ; Autoimmunity ; Antigens, CD20 ; Central Nervous System ; B-Lymphocytes ; Encephalomyelitis, Autoimmune, Experimental ; Multiple Sclerosis ; Meninges ; Antibodies
    Chemische Substanzen Antigens, CD20 ; Antibodies
    Sprache Englisch
    Erscheinungsdatum 2023-12-15
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 8335-5
    ISSN 1872-8421 ; 0165-5728
    ISSN (online) 1872-8421
    ISSN 0165-5728
    DOI 10.1016/j.jneuroim.2023.578267
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

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  2. Artikel ; Online: Activated B Cells Participating in the Anti-Myelin Response Are Excluded from the Inflamed Central Nervous System in a Model of Autoimmunity that Allows for B Cell Recognition of Autoantigen.

    Tesfagiorgis, Yodit / Zhu, Sarah L / Jain, Rajiv / Kerfoot, Steven M

    Journal of immunology (Baltimore, Md. : 1950)

    2017  Band 199, Heft 2, Seite(n) 449–457

    Abstract: Once activated, T cells gain the ability to access both healthy and inflamed nonlymphoid tissues. They are then reactivated to remain in the tissue and exert their effector function only if they encounter their specific Ag. In this study, we set out to ... ...

    Abstract Once activated, T cells gain the ability to access both healthy and inflamed nonlymphoid tissues. They are then reactivated to remain in the tissue and exert their effector function only if they encounter their specific Ag. In this study, we set out to determine if the same is true for B cells using a mouse model of CNS autoimmunity that incorporates both T and B cell recognition of a myelin autoantigen. Both T and B cells were common infiltrates of spinal cords in diseased mice. However, unlike T cells, anti-myelin B cells were excluded from the inflamed tissue. Further, CNS B cells did not have a phenotype consistent with Ag-specific activation as it occurs in lymphatic tissue. Instead, they expressed elevated levels of CD80, indicating that B cells may contribute to local inflammation through nonantigen-specific mechanisms.
    Mesh-Begriff(e) Animals ; Autoantigens/immunology ; Autoimmunity ; B-Lymphocytes/immunology ; B-Lymphocytes/physiology ; B7-1 Antigen/genetics ; B7-1 Antigen/immunology ; Cell Movement/immunology ; Central Nervous System/immunology ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Inflammation/immunology ; Lymphocyte Activation ; Lymphoid Tissue/immunology ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/immunology ; Spinal Cord/immunology ; Spinal Cord/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes/physiology
    Chemische Substanzen Autoantigens ; B7-1 Antigen
    Sprache Englisch
    Erscheinungsdatum 2017-07-15
    Erscheinungsland United States
    Dokumenttyp Journal Article
    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.1602042
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: F4/80

    Shin, Alice E / Tesfagiorgis, Yodit / Larsen, Frederikke / Derouet, Mathieu / Zeng, Peter Y F / Good, Hayley J / Zhang, Liyue / Rubinstein, Mara R / Han, Yiping W / Kerfoot, Steven M / Nichols, Anthony C / Hayakawa, Yoku / Howlett, Christopher J / Wang, Timothy C / Asfaha, Samuel

    Gastroenterology

    2023  Band 164, Heft 4, Seite(n) 593–609.e13

    Abstract: Background & aims: Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood.! ...

    Abstract Background & aims: Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood.
    Methods: To investigate whether different forms of inflammation pose the same risk of cancer, we compared several murine models of colitis (dextran sodium sulfate [DSS], 2,4,6-trinitrobenzene sulfonic acid, 4-ethoxylmethylene-2-phenyloxazol-5-one, Citrobacter rodentium, Fusobacterium nucleatum, and doxorubicin) with respect to their ability to lead to colonic tumorigenesis. We attempted to correlate the severity of colitis and inflammatory profile with the risk of tumorigenesis in both azoxymethane-dependent and Dclk1/APC
    Results: DSS colitis reproducibly led to colonic tumors in both mouse models of colitis-associated cancer. In contrast, all other forms of colitis did not lead to cancer. When compared with the colitis not associated with tumorigenesis, DSS colitis was characterized by significantly increased CD11b
    Conclusions: We have identified CD11b
    Mesh-Begriff(e) Animals ; Mice ; Azoxymethane ; Carcinogenesis/metabolism ; Cell Plasticity ; Colitis/chemically induced ; Colitis/complications ; Colitis/metabolism ; Colitis-Associated Neoplasms/metabolism ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Inflammation/metabolism ; Macrophages/metabolism ; Mice, Inbred C57BL
    Chemische Substanzen Azoxymethane (MO0N1J0SEN) ; Dextran Sulfate (9042-14-2) ; Ly-6C antigen, mouse
    Sprache Englisch
    Erscheinungsdatum 2023-01-10
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2023.01.002
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Autoreactive, Low-Affinity T Cells Preferentially Drive Differentiation of Short-Lived Memory B Cells at the Expense of Germinal Center Maintenance.

    Jain, Rajiv W / Parham, Kate A / Tesfagiorgis, Yodit / Craig, Heather C / Romanchik, Emiliano / Kerfoot, Steven M

    Cell reports

    2018  Band 25, Heft 12, Seite(n) 3342–3355.e5

    Abstract: B cell fate decisions within a germinal center (GC) are critical to determining the outcome of the immune response to a given antigen. Here, we characterize GC kinetics and B cell fate choices in a response to the autoantigen myelin oligodendrocyte ... ...

    Abstract B cell fate decisions within a germinal center (GC) are critical to determining the outcome of the immune response to a given antigen. Here, we characterize GC kinetics and B cell fate choices in a response to the autoantigen myelin oligodendrocyte glycoprotein (MOG) and compare the response with a standard model foreign antigen. Both antigens generate productive primary responses, as evidenced by GC development, circulating antigen-specific antibodies, and differentiation of memory B cells. However, in the MOG response, the status of the cognate T cell partner drives preferential B cell differentiation to a memory phenotype at the expense of GC maintenance, resulting in a truncated GC. Reduced plasma cell differentiation is largely independent of T cell influence. Interestingly, memory-phenotype B cells formed in the MOG GC are not long lived, resulting in a failure of the B cell response to secondary challenge.
    Mesh-Begriff(e) Animals ; Antigens, CD/metabolism ; Autoantigens/metabolism ; B-Lymphocytes/cytology ; Cell Differentiation ; Germinal Center/immunology ; Haptens/metabolism ; Immunization ; Immunologic Memory ; Lymphocyte Activation/immunology ; Mice, Inbred C57BL ; Mice, Transgenic ; Myelin-Oligodendrocyte Glycoprotein/metabolism ; Ovalbumin/metabolism ; Phenotype ; T-Lymphocytes/cytology ; T-Lymphocytes/metabolism
    Chemische Substanzen Antigens, CD ; Autoantigens ; Haptens ; Myelin-Oligodendrocyte Glycoprotein ; Ovalbumin (9006-59-1)
    Sprache Englisch
    Erscheinungsdatum 2018-12-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2018.11.070
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Opposing Roles for the Related ETS-Family Transcription Factors Spi-B and Spi-C in Regulating B Cell Differentiation and Function.

    Laramée, Anne-Sophie / Raczkowski, Hannah / Shao, Peng / Batista, Carolina / Shukla, Devanshi / Xu, Li / Haeryfar, S M Mansour / Tesfagiorgis, Yodit / Kerfoot, Steven / DeKoter, Rodney

    Frontiers in immunology

    2020  Band 11, Seite(n) 841

    Abstract: Generation of specific antibodies during an immune response to infection or vaccination depends on the ability to rapidly and accurately select clones of antibody-secreting B lymphocytes for expansion. Antigen-specific B cell clones undergo the cell fate ...

    Abstract Generation of specific antibodies during an immune response to infection or vaccination depends on the ability to rapidly and accurately select clones of antibody-secreting B lymphocytes for expansion. Antigen-specific B cell clones undergo the cell fate decision to differentiate into antibody-secreting plasma cells, memory B cells, or germinal center B cells. The E26-transformation-specific (ETS) transcription factors Spi-B and Spi-C are important regulators of B cell development and function. Spi-B is expressed throughout B cell development and is downregulated upon plasma cell differentiation. Spi-C is highly related to Spi-B and has similar DNA-binding specificity. Heterozygosity for
    Mesh-Begriff(e) Animals ; B-Lymphocytes/immunology ; Cell Differentiation/immunology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation/immunology ; Mice ; Mice, Knockout ; Proto-Oncogene Proteins c-ets/genetics ; Proto-Oncogene Proteins c-ets/metabolism ; Spleen/cytology ; Spleen/immunology ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemische Substanzen DNA-Binding Proteins ; Proto-Oncogene Proteins c-ets ; Spi-B protein, mouse ; Spic protein, mouse ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2020-05-08
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.00841
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of CNS Autoimmune Disease.

    Dang, Amy K / Tesfagiorgis, Yodit / Jain, Rajiv W / Craig, Heather C / Kerfoot, Steven M

    Frontiers in immunology

    2015  Band 6, Seite(n) 470

    Abstract: We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte ... ...

    Abstract We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4(+) T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to the meninges, often in clusters reminiscent of those described in human multiple sclerosis. These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course. Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35(+) follicular dendritic cells, or germinal centers. The majority of cluster B cells were IgD(+) with little evidence of class switch. Consistent with this, B cells isolated from the spinal cord were of the naïve/memory CD38(hi) CD95(lo) phenotype. Nevertheless, they were CD62L(lo) and CD80(hi) compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen. Therefore, if meningeal B cells contribute to CNS pathology in autoimmunity, follicular differentiation is not necessary for the pathogenic mechanism.
    Sprache Englisch
    Erscheinungsdatum 2015
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2015.00470
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitis.

    Whittaker Hawkins, Ryder F / Patenaude, Alexandre / Dumas, Aline / Jain, Rajiv / Tesfagiorgis, Yodit / Kerfoot, Steven / Matsui, Takeshi / Gunzer, Matthias / Poubelle, Patrice E / Larochelle, Catherine / Pelletier, Martin / Vallières, Luc

    JCI insight

    2017  Band 2, Heft 23

    Abstract: Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during ... ...

    Abstract Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation. In corroboration, super-resolution (3D stimulated emission-depletion [STED]) microscopy revealed neutrophils forming synapses with T and B cells in situ. Further, neutrophils specifically express the aspartic retroviral-like protease ASPRV1, which increases in the CNS during EAE and severe cases of multiple sclerosis. Without ASPRV1, mice immunized with a new B cell-dependent myelin antigen (but not with the traditional myelin oligodendrocyte glycoprotein peptide) develop a chronic phase of EAE that is less severe and even completely fades in many individuals. Therefore, ICAM1+ macrophage-like neutrophils can play both shared and nonredundant roles in autoimmune demyelination, among them perpetuating inflammation via ASPRV1.
    Mesh-Begriff(e) Animals ; Antigen Presentation/immunology ; Aspartic Acid Endopeptidases/immunology ; B-Lymphocytes/immunology ; Chronic Disease ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Immunological Synapses/immunology ; Immunophenotyping ; Intercellular Adhesion Molecule-1/metabolism ; Mice, Inbred C57BL ; Neutrophils/immunology ; Spinal Cord/immunology ; T-Lymphocytes/immunology ; Transcriptome/immunology
    Chemische Substanzen Icam1 protein, mouse ; Taps protein, mouse ; Intercellular Adhesion Molecule-1 (126547-89-5) ; Aspartic Acid Endopeptidases (EC 3.4.23.-)
    Sprache Englisch
    Erscheinungsdatum 2017-12-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.96882
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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