دورية أكاديمية
TIM4 regulates the anti-islet Th2 alloimmune response
| العنوان: | TIM4 regulates the anti-islet Th2 alloimmune response |
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| المؤلفون: | Vergani, Andrea, Gatti, Francesca, Lee, Kang Mi, D’Addio, Francesca, Sara,Tezza, Chin, Melissa, Bassi, Roberto, Tian, Ze, Wu, Ex, Maffi, Paola, Ben, Nasr, Kim, Ji, Secchi, A, Markmann, James F, Turka, Laurance, Rothstein, David M, Sayegh, Mohamed H, Paolo, Fiorina |
| المساهمون: | Vergani, Andrea, Gatti, Francesca, Lee, Kang Mi, D’Addio, Francesca, Sara, Tezza, Chin, Melissa, Bassi, Roberto, Tian, Ze, Wu, Ex, Maffi, Paola, Ben, Nasr, Kim, Ji, Secchi, A, Markmann, James F, Turka, Laurance, Rothstein, David M, Sayegh, Mohamed H, Paolo, Fiorina |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Autoimmune diabete, Costimulatory molecule, Islet transplantation, Regulatory cell, Adult, Animal, B-Lymphocyte, Cell Differentiation, Cytokine, Diabetes Mellitus, Experimental, Type 1, Female, Graft Survival, Human, Islets of Langerhan, Islets of Langerhans Transplantation, Male, Membrane Protein, Mice, Inbred BALB C, Inbred C57BL, Inbred NOD, Middle Aged, Survival Rate, Th1 Cell, Th2 Cell, Transcriptome, Transplantation, Homologou |
| الوصف: | The role of the novel costimulatory molecule TIM4 in anti-islet response is unknown. We explored TIM4 expression and targeting in Th1 (BALB/c islets into C57BL/6 mice) and Th2 (BALB/c islets into Tbet-/- C57BL/6 mice) models of anti-islet alloimmune response and in a model of anti-islet autoimmune response (diabetes onset in NOD mice). The targeting of TIM4, using the monoclonal antibody RMT4-53, promotes islet graft survival in a Th1 model, with 30% of the graft surviving in the long term; islet graft protection appears to be mediated by a Th1 to Th2 skewing of the immune response. Differently, in the Th2 model, TIM4 targeting precipitates graft rejection by further enhancing the Th2 response. The effect of anti-TIM4 treatment in preventing autoimmune diabetes was marginal with only minor Th1 to Th2 skewing. B-Cell depletion abolished the effect of TIM4 targeting. TIM4 is expressed on human B-cells and is upregulated in diabetic and islettransplanted patients. Our data suggest a model in which TIM4 targeting promotes Th2 response over Th1 via B-cells. The targeting of TIM4 could become a component of an immunoregulatory protocol in clinical islet transplantation, aiming at redirecting the immune system toward a Th2 response. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English Italian |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/WOS:000359878900014; volume:24; issue:8; firstpage:1599; lastpage:1614; numberofpages:16; journal:CELL TRANSPLANTATION; http://hdl.handle.net/20.500.11768/15718Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84938862640; http://www.ingentaconnect.com/search/download?pub=infobike://cog/ct/2015/00000024/00000008/art00014&mimetype=application/pdfTest |
| DOI: | 10.3727/096368914X678571 |
| الإتاحة: | https://doi.org/20.500.11768/15718Test https://doi.org/10.3727/096368914X678571Test https://hdl.handle.net/20.500.11768/15718Test http://www.ingentaconnect.com/search/download?pub=infobike://cog/ct/2015/00000024/00000008/art00014&mimetype=application/pdfTest |
| رقم الانضمام: | edsbas.EE07D6F2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3727/096368914X678571 |
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