المؤلفون: Sahin, Mehmet, Remy, Mélissa, Fallet, Bénédict, Sommerstein, Rami, Florova, Marianna, Langner, Anna, Klausz, Katja, Straub, Tobias, Kreutzfeldt, Mario, Wagner, Ingrid, Schmidt, Cinzia T, Malinge, Pauline, Magistrelli, Giovanni, Izui, Shozo, Pircher, Hanspeter, Verbeek, J Sjef, Merkler, Doron, Peipp, Matthias, Pinschewer, Daniel

المصدر: ISSN: 2211-1247 ; Cell reports, vol. 38, no. 5 (2022) 110303.

مصطلحات موضوعية: info:eu-repo/classification/ddc/616.07, Fc gamma receptors, Antibody bivalency, Antiviral protection, Humoral immunity, Immunoglobulin superfamily, Inhibition of virion release, Lymphocytic choriomeningitis virus (LCMV), Virus budding, Virus neutralization, Animals, Antibodies, Neutralizing / immunology, Neutralizing / pharmacology, Viral / immunology, Viral / pharmacology, Antiviral Agents / pharmacology, Epitopes / drug effects, Epitopes / immunology, HIV Antibodies / immunology, HIV Antibodies / pharmacology, Immunoglobulin G / drug effects, Immunoglobulin G / immunology, Mice, Inbred C57BL, Receptors, Fc / drug effects, IgG / drug effects, IgG / immunology

الوصف: Across the animal kingdom, multivalency discriminates antibodies from all other immunoglobulin superfamily members. The evolutionary forces conserving multivalency above other structural hallmarks of antibodies remain, however, incompletely defined. Here, we engineer monovalent either Fc-competent or -deficient antibody formats to investigate mechanisms of protection of neutralizing antibodies (nAbs) and non-neutralizing antibodies (nnAbs) in virus-infected mice. Antibody bivalency enables the tethering of virions to the infected cell surface, inhibits the release of virions in cell culture, and suppresses viral loads in vivo independently of Fc gamma receptor (FcγR) interactions. In return, monovalent antibody formats either do not inhibit virion release and fail to protect in vivo or their protective efficacy is largely FcγR dependent. Protection in mice correlates with virus-release-inhibiting activity of nAb and nnAb rather than with their neutralizing capacity. These observations provide mechanistic insights into the evolutionary conservation of antibody bivalency and help refining correlates of nnAb protection for vaccine development.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35108544; info:eu-repo/grantAgreement/EC/H2020/865026/EU/Molecular pathology of anti-viral T cell responses in the central nervous system/PATHOCODE; info:eu-repo/grantAgreement/EC/FP7/310962/EU/Memory B cell immunity in chronic viral infection/IMMUNIBY; https://archive-ouverte.unige.ch/unige:166485Test; unige:166485

الإتاحة: https://doi.org/10.1016Test/j.celrep.2022.110303
https://archive-ouverte.unige.ch/unige:166485Test

المؤلفون: Legrain, Sarah, Su, Dan, Gaignage, Mélanie, Breukel, Cor, Claassens, Jill, Brouwers, Conny, Linssen, Margot M, Izui, Shozo, Verbeek, J Sjef, Coutelier, Jean-Paul

المساهمون: UCL - SSS/DDUV/MEXP - Médecine expérimentale

المصدر: International Journal of Molecular Sciences, Vol. 22, no. 16, p. 9027 (2021)

الوصف: Infection with viruses, such as the lactate dehydrogenase-elevating virus (LDV), is known to trigger the onset of autoimmune anemia through the enhancement of the phagocytosis of autoantibody-opsonized erythrocytes by activated macrophages. Type I interferon receptor-deficient mice show enhanced anemia, which suggests a protective effect of these cytokines, partly through the control of type II interferon production. The development of anemia requires the expression of Fcγ receptors (FcγR) I, III, and IV. Whereas LDV infection decreases FcγR III expression, it enhances FcγR I and IV expression in wild-type animals. The LDV-associated increase in the expression of FcγR I and IV is largely reduced in type I interferon receptor-deficient mice, through both type II interferon-dependent and -independent mechanisms. Thus, the regulation of the expression of FcγR I and IV, but not III, by interferons may partly explain the exacerbating effect of LDV infection on anemia that results from the enhanced phagocytosis of IgG autoantibody-opsonized erythrocytes.

العلاقة: boreal:255554; http://hdl.handle.net/2078.1/255554Test

الإتاحة: https://doi.org/10.3390/ijms22169027Test
http://hdl.handle.net/2078.1/255554Test

المؤلفون: Sow, Heng Sheng, Benonisson, Hreinn, Brouwers, Conny, Linssen, Margot M., Camps, Marcel, Breukel, Cor, Claassens, Jill, van Hall, Thorbald, Ossendorp, Ferry, Fransen, Marieke F., Verbeek, J. Sjef

المصدر: Sow , H S , Benonisson , H , Brouwers , C , Linssen , M M , Camps , M , Breukel , C , Claassens , J , van Hall , T , Ossendorp , F , Fransen , M F & Verbeek , J S 2020 , ' Immunogenicity of rat-neu + mouse mammary tumours determines the T cell-dependent therapeutic efficacy of anti-neu monoclonal antibody treatment ' , Scientific Reports , vol. 10 , no. 1 , 3933 . https://doi.org/10.1038/s41598-020-60893-8Test

الوصف: The use of Trastuzumab (Herceptin), a monoclonal antibody (mAb) targeting HER2/neu, results in an increased median survival in Her2 + breast cancer patients. The tumour mutational burden and the presence of tumour infiltrating lymphocytes (TILs) clearly correlate with response to trastuzumab. Here, we investigated if the immunogenicity of the transplantable rat-neu + tumour cell line (TUBO) derived from a BALB/c-NeuT primary tumour is associated with the response to anti-neu mAb therapy. We compared the TUBO tumour outgrowth and tumour infiltrating T cells in isogenic (BALB/c-NeuT) and non-isogenic (WT BALB/c) recipient mice. Furthermore, therapeutic efficacy of anti-neu mAb and the contribution of T cells were examined in both mouse strains. The outgrowth of untreated tumours was significantly better in BALB/c-NeuT than WT BALB/c mice. Moreover, tumour infiltrating T cells were more abundantly present in WT BALB/c than BALB/c-NeuT mice, showing that the TUBO tumour was more immunogenic in WT BALB/c mice. In TUBO tumour bearing WT BALB/c mice, anti-neu mAb therapy resulted in an increase of tumour infiltrating T cells and long-term survival. When T cells were depleted, this strong anti-tumour effect was reduced to an outgrowth delay. In contrast, in TUBO tumour bearing BALB/c-NeuT mice, treatment with anti-neu mAb resulted only in tumour outgrowth delay, both in the presence and absence of T cells. We concluded that in immunogenic tumours the response to anti-neu mAb therapy is enhanced by additional T cell involvement compared to the response to anti-neu mAb in non-immunogenic tumours.

العلاقة: https://research.vumc.nl/en/publications/8cf52725-66de-497d-b820-29a3c94ff100Test

الإتاحة: https://doi.org/10.1038/s41598-020-60893-8Test
https://research.vumc.nl/en/publications/8cf52725-66de-497d-b820-29a3c94ff100Test
http://www.scopus.com/inward/record.url?scp=85081042363&partnerID=8YFLogxKTest

المؤلفون: Yu, Xiaojie, Chan, H. T.Claude, Fisher, Hayden, Penfold, Christine A., Kim, Jinny, Inzhelevskaya, Tatyana, Mockridge, C. Ian, French, Ruth R., Duriez, Patrick J., Douglas, Leon R., English, Vikki, Verbeek, J. Sjef, White, Ann L., Tews, Ivo, Glennie, Martin J., Cragg, Mark S.

الوصف: Anti-CD40 monoclonal antibodies (mAbs) comprise agonists and antagonists, which display promising therapeutic activities in cancer and autoimmunity, respectively. We previously showed that epitope and isotype interact to deliver optimal agonistic anti-CD40 mAbs. The impact of Fc engineering on antagonists, however, remains largely unexplored. Here, we show that clinically relevant antagonists used for treating autoimmune conditions can be converted into potent FcγR-independent agonists with remarkable antitumor activity by isotype switching to hIgG2. One antagonist is converted to a super-agonist with greater potency than previously reported highly agonistic anti-CD40 mAbs. Such conversion is dependent on the unique disulfide bonding properties of the hIgG2 hinge. This investigation highlights the transformative capacity of the hIgG2 isotype for converting antagonists to agonists to treat cancer.

وصف الملف: text

العلاقة: https://eprints.soton.ac.uk/441073/1/1_s2.0_S1535610820302129_main.pdfTest; https://eprints.soton.ac.uk/441073/2/CANCER_CELL_D_19_00994_R5authorsubmitted.pdfTest; Yu, Xiaojie, Chan, H. T.Claude, Fisher, Hayden, Penfold, Christine A., Kim, Jinny, Inzhelevskaya, Tatyana, Mockridge, C. Ian, French, Ruth R., Duriez, Patrick J., Douglas, Leon R., English, Vikki, Verbeek, J. Sjef, White, Ann L., Tews, Ivo, Glennie, Martin J. and Cragg, Mark S. (2020) Isotype switching converts anti-CD40 antagonism to agonism to elicit potent antitumor activity. Cancer Cell, 37 (6), 850-866.e7. (doi:10.1016/j.ccell.2020.04.013 ).

الإتاحة: https://doi.org/10.1016Test/j.ccell.2020.04.013
https://eprints.soton.ac.uk/441073Test/
https://eprints.soton.ac.uk/441073/1/1_s2.0_S1535610820302129_main.pdfTest
https://eprints.soton.ac.uk/441073/2/CANCER_CELL_D_19_00994_R5authorsubmitted.pdfTest

المؤلفون: Koelink, Pim J, Bloemendaal, Felicia M, Li, Bofeng, Westera, Liset, Vogels, Esther W M, van Roest, Manon, Gloudemans, Anouk K, van 't Wout, Angelique B, Korf, Hannelie, Vermeire, Séverine, te Velde, Anje A, Ponsioen, Cyriel Y, D'Haens, Geert RAM, Verbeek, J Sjef, Geiger, Terrence L, Wildenberg, Manon E, van den Brink, Gijs R

مصطلحات موضوعية: Inflammatory bowel disease

الوصف: Objective Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined. Design We used human peripheral blood monocytes and mouse bone marrow-derived macrophages to study IL-10 production and CD206+ regulatory macrophage differentiation. To determine whether the efficacy of anti-TNF was dependent on IL-10 signalling in vivo and in which cell type, we used the CD4+CD45Rbhigh T-cell transfer model in combination with several genetic mouse models. Results Anti-TNF therapy increased macrophage IL-10 production in an FcγR-dependent manner, which caused differentiation of macrophages to a more regulatory CD206+ phenotype in vitro. Pharmacological blockade of IL-10 signalling prevented the induction of these CD206+ regulatory macrophages and diminished the therapeutic efficacy of anti-TNF therapy in the CD4+CD45Rbhigh T-cell transfer model of IBD. Using cell type-specific IL-10 receptor mutant mice, we found that IL-10 signalling in macrophages but not T cells was critical for the induction of CD206+ regulatory macrophages and therapeutic response to anti-TNF. Conclusion The therapeutic efficacy of anti-TNF in resolving intestinal inflammation is critically dependent on IL-10 signalling in macrophages.

وصف الملف: text/html

العلاقة: http://gut.bmj.com/cgi/content/short/69/6/1053Test; http://dx.doi.org/10.1136/gutjnl-2019-318264Test

الإتاحة: https://doi.org/10.1136/gutjnl-2019-318264Test
http://gut.bmj.com/cgi/content/short/69/6/1053Test

المؤلفون: Schweier, Oliver, Aichele, Ulrike, Marx, Anna‐Friederike, Straub, Tobias, Verbeek, J. Sjef, Pinschewer, Daniel D., Pircher, Hanspeter

المساهمون: Deutsche Forschungsgemeinschaft

المصدر: European Journal of Immunology ; volume 49, issue 4, page 626-637 ; ISSN 0014-2980 1521-4141

الوصف: Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (Arm) induces an acute infection with rapid virus clearance by CD8 + T cells independently of CD4 + T cell help. Residual viral antigen may, however, persist for a prolonged time. Here, we demonstrate that mice that had been transiently depleted of CD4 + T cells during acute LCMV Arm infection generated high levels of virus‐specific IgG antibodies (Ab) after viral clearance. Robust induction of LCMV‐specific IgG after transient CD4 + T cell depletion was dependent on Fcγ receptors but not on the complement receptors CD21/CD35. In contrast to the potent production of LCMV‐specific IgG, the generation of LCMV‐specific isotype‐switched memory B cells after transient CD4 + T cell depletion was considerably reduced. Moreover, mice depleted of CD4 + T cells during acute infection were strongly impaired in generating a secondary LCMV‐specific B cell response upon LCMV rechallenge. In conclusion, our data indicate that LCMV antigen depots after viral clearance were capable of inducing high levels of virus‐specific IgG. They failed, however, to induce robust virus‐specific B cell memory revealing a previously unappreciated dichotomy of specific Ab production and memory cell formation after priming with residual antigen.

الإتاحة: https://doi.org/10.1002/eji.201847772Test

المؤلفون: Kleinovink, Jan Willem, Mezzanotte, Laura, Zambito, Giorgia, Fransen, Marieke F, Cruz, Luis J, Verbeek, J Sjef, Chan, Alan, Ossendorp, Ferry, Löwik, Clemens

المصدر: Kleinovink , J W , Mezzanotte , L , Zambito , G , Fransen , M F , Cruz , L J , Verbeek , J S , Chan , A , Ossendorp , F & Löwik , C 2019 , ' A Dual-Color Bioluminescence Reporter Mouse for Simultaneous in vivo Imaging of T Cell Localization and Function ' , Frontiers in Immunology , vol. 9 , 3097 . https://doi.org/10.3389/fimmu.2018.03097Test

مصطلحات موضوعية: /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMGC011203, name=EMC MGC-01-12-03, /dk/atira/pure/keywords/researchprograms/AFL001000/EMCNIHES033003, name=EMC NIHES-03-30-03, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being

الوصف: Non-invasive imaging technologies to visualize the location and functionality of T cells are of great value in immunology. Here, we describe the design and generation of a transgenic mouse in which all T cells constitutively express green-emitting click-beetle luciferase (CBG99) while expression of the red-emitting firefly luciferase (PpyRE9) is induced by Nuclear Factor of Activated T cells (NFAT) such as during T cell activation, which allows multicolor bioluminescence imaging of T cell location and function. This dual-luciferase mouse, which we named TbiLuc, showed high constitutive luciferase expression in lymphoid organs such as lymph nodes and the spleen. Ex vivo purified CD8+ and CD4+ T cells both constitutively expressed luciferase, whereas B cells showed no detectable signal. We cross-bred TbiLuc mice to T cell receptor-transgenic OT-I mice to obtain luciferase-expressing naïve CD8+ T cells with defined antigen-specificity. TbiLuc*OT-I T cells showed a fully antigen-specific induction of the T cell activation-dependent luciferase. In vaccinated mice, we visualized T cell localization and activation in vaccine-draining lymph nodes with high sensitivity using two distinct luciferase substrates, D-luciferin and CycLuc1, of which the latter specifically reacts with the PpyRE9 enzyme. This dual-luciferase T cell reporter mouse can be applied in many experimental models studying the location and functional state of T cells.

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/cd8a9fc8-81e2-4390-b863-ce067f81c734Test

الإتاحة: https://doi.org/10.3389/fimmu.2018.03097Test
https://pure.eur.nl/en/publications/cd8a9fc8-81e2-4390-b863-ce067f81c734Test
https://pure.eur.nl/ws/files/81553010/A_Dual_Color_Bioluminescence_Reporter_Mouse_for_Simultaneous_in_vivo_Imaging_of_T_Cell_Localization_and_Function.pdfTest

المؤلفون: Hirose, Sachiko, Lin, Qingshun, Ohtsuji, Mareki, Nishimura, Hiroyuki, Verbeek, J Sjef

المساهمون: Ministry of Education, Culture, Science, Sports, Science and Technology of Japan, Ministry of Health, Labour and Welfare, Japan Society for the Promotion of Science, FY2017 JSPS International Fellowship for Research

المصدر: International Immunology ; volume 31, issue 11, page 687-696 ; ISSN 1460-2377

الوصف: AbstractMonocytes are evolutionally conserved innate immune cells that play essential roles for the protection of the host against pathogens and also produce several inflammatory cytokines. Thus, the aberrant functioning of monocytes may affect not only host defense but also the development of inflammatory diseases. Monocytes are a heterogeneous population with phenotypical and functional differences. Most recent studies have shown that monocytes are divided into three subsets, namely classical, intermediate and non-classical subsets, both in humans and mice. Accumulating evidence showed that monocyte activation is associated with the disease progression in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, it remains to be determined how monocytes contribute to the disease process and which subset is involved. In this review, we discuss the pathogenic role of monocyte subsets in SLE and RA on the basis of current studies by ourselves and others to shed light on the suitability of monocyte-targeted therapies in these diseases.

الإتاحة: https://doi.org/10.1093/intimm/dxz036Test
https://academic.oup.com/intimm/article-pdf/31/11/687/54093518/dxz036.pdfTest

المؤلفون: Koelink, Pim J, Bloemendaal, Felicia M, Li, Bofeng, Westera, Liset, Vogels, Esther W M, van Roest, Manon, Gloudemans, Anouk K, van 't Wout, Angelique B, Korf, Hannelie, Vermeire, Séverine, te Velde, Anje A, Ponsioen, Cyriel Y, D'Haens, Geert RAM, Verbeek, J Sjef, Geiger, Terrence L, Wildenberg, Manon E, van den Brink, Gijs R

المصدر: Gut ; volume 69, issue 6, page 1053-1063 ; ISSN 0017-5749 1468-3288

الوصف: Objective Macrophage interleukin (IL)-10 signalling plays a critical role in the maintenance of a regulatory phenotype that prevents the development of IBD. We have previously found that anti-tumour necrosis factor (TNF) monoclonal antibodies act through Fcγ-receptor (FcγR) signalling to promote repolarisation of proinflammatory intestinal macrophages to a CD206+ regulatory phenotype. The role of IL-10 in anti-TNF-induced macrophage repolarisation has not been examined. Design We used human peripheral blood monocytes and mouse bone marrow-derived macrophages to study IL-10 production and CD206+ regulatory macrophage differentiation. To determine whether the efficacy of anti-TNF was dependent on IL-10 signalling in vivo and in which cell type, we used the CD4+CD45Rb high T-cell transfer model in combination with several genetic mouse models. Results Anti-TNF therapy increased macrophage IL-10 production in an FcγR-dependent manner, which caused differentiation of macrophages to a more regulatory CD206+ phenotype in vitro. Pharmacological blockade of IL-10 signalling prevented the induction of these CD206+ regulatory macrophages and diminished the therapeutic efficacy of anti-TNF therapy in the CD4+CD45Rb high T-cell transfer model of IBD. Using cell type-specific IL-10 receptor mutant mice, we found that IL-10 signalling in macrophages but not T cells was critical for the induction of CD206+ regulatory macrophages and therapeutic response to anti-TNF. Conclusion The therapeutic efficacy of anti-TNF in resolving intestinal inflammation is critically dependent on IL-10 signalling in macrophages.

الإتاحة: https://doi.org/10.1136/gutjnl-2019-318264Test

المؤلفون: Verbeek, J. Sjef, Hirose, Sachiko, Nishimura, Hiroyuki

المصدر: Frontiers in Immunology ; volume 10 ; ISSN 1664-3224

الإتاحة: https://doi.org/10.3389/fimmu.2019.02061Test