The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform

Rafi Ahmed - One of the best experts on this subject based on the ideXlab platform.

  • mtor regulates memory cd8 t Cell Differentiation
    Nature, 2009
    Co-Authors: Koichi Araki, Alexandra P. Turner, Shivaprakash Gangappa, Susanne A. Keller, Virginia Oliva Shaffer, Christian P. Larsen, Martin F. Bachmann, Rafi Ahmed
    Abstract:

    mTOR, part of the PI3K–AKT–mTOR Cell-signalling cascade and a target for the antitumour drug rapamycin, is identified here as a regulator of CD8 T-Cell Differentiation. Despite its primarily immunosuppressive activity, rapamycin can enhance immune responses to experimental vaccines in mice and monkeys. This counterintuitive finding points to the ability to increase the functional qualities of memory T Cells as a potential way of enhancing the efficacy of vaccines against pathogens and cancers. Inducing effective memory T-Cell responses is a major goal of vaccines against chronic infections and tumours. Here, mTOR, the mammalian target for the immunosuppressive drug rapamycin, is shown to enhance the quantity and quality of virus-specific CD8 T Cells in mouse and non-human primate models. Memory CD8 T Cells are a critical component of protective immunity, and inducing effective memory T-Cell responses is a major goal of vaccines against chronic infections and tumours1,2,3. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T Cells4. Here we show that mTOR (mammalian target of rapamycin5, also known as FRAP1) is a major regulator of memory CD8 T-Cell Differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T Cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T Cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-Cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-Cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-Cell Differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T Cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-Cell Differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T Cells.

  • mTOR regulates memory CD8 T-Cell Differentiation
    Nature, 2009
    Co-Authors: Koichi Araki, Alexandra P. Turner, Shivaprakash Gangappa, Susanne A. Keller, Virginia Oliva Shaffer, Christian P. Larsen, Martin F. Bachmann, Rafi Ahmed
    Abstract:

    Memory CD8 T Cells are a critical component of protective immunity, and inducing effective memory T-Cell responses is a major goal of vaccines against chronic infections and tumours. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T Cells. Here we show that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-Cell Differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T Cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T Cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-Cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-Cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-Cell Differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T Cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-Cell Differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T Cells.

Kuo-i Lin - One of the best experts on this subject based on the ideXlab platform.

  • SUMOylation of Blimp-1 is critical for plasma Cell Differentiation
    EMBO Reports, 2012
    Co-Authors: Hsia Yuan Ying, Shin Tang Su, Pang Hung Hsu, Che Chang Chang, I. Ying Lin, Yu Hsuan Tseng, Hsiu Ming Shih, Ming-daw Tsai, Kuo-i Lin
    Abstract:

    Transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) is a master regulator of plasma Cell Differentiation. Here we show that Blimp-1 is covalently modified by SUMO1 at lysine 816, a modification mediated by SUMO E3 ligase PIAS1. Mutation of Blimp-1 lysine 816 reduces transcriptional repression--correlating with a reduced interaction with a histone deacetylase, HDAC2--and impairs Differentiation of antibody-secreting Cells. Thus, the SUMO pathway critically regulates Blimp-1 function during plasma Cell Differentiation.

Koichi Araki - One of the best experts on this subject based on the ideXlab platform.

  • mtor regulates memory cd8 t Cell Differentiation
    Nature, 2009
    Co-Authors: Koichi Araki, Alexandra P. Turner, Shivaprakash Gangappa, Susanne A. Keller, Virginia Oliva Shaffer, Christian P. Larsen, Martin F. Bachmann, Rafi Ahmed
    Abstract:

    mTOR, part of the PI3K–AKT–mTOR Cell-signalling cascade and a target for the antitumour drug rapamycin, is identified here as a regulator of CD8 T-Cell Differentiation. Despite its primarily immunosuppressive activity, rapamycin can enhance immune responses to experimental vaccines in mice and monkeys. This counterintuitive finding points to the ability to increase the functional qualities of memory T Cells as a potential way of enhancing the efficacy of vaccines against pathogens and cancers. Inducing effective memory T-Cell responses is a major goal of vaccines against chronic infections and tumours. Here, mTOR, the mammalian target for the immunosuppressive drug rapamycin, is shown to enhance the quantity and quality of virus-specific CD8 T Cells in mouse and non-human primate models. Memory CD8 T Cells are a critical component of protective immunity, and inducing effective memory T-Cell responses is a major goal of vaccines against chronic infections and tumours1,2,3. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T Cells4. Here we show that mTOR (mammalian target of rapamycin5, also known as FRAP1) is a major regulator of memory CD8 T-Cell Differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T Cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T Cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-Cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-Cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-Cell Differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T Cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-Cell Differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T Cells.

  • mTOR regulates memory CD8 T-Cell Differentiation
    Nature, 2009
    Co-Authors: Koichi Araki, Alexandra P. Turner, Shivaprakash Gangappa, Susanne A. Keller, Virginia Oliva Shaffer, Christian P. Larsen, Martin F. Bachmann, Rafi Ahmed
    Abstract:

    Memory CD8 T Cells are a critical component of protective immunity, and inducing effective memory T-Cell responses is a major goal of vaccines against chronic infections and tumours. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T Cells. Here we show that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-Cell Differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T Cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T Cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-Cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-Cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-Cell Differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T Cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-Cell Differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T Cells.

G M Doody - One of the best experts on this subject based on the ideXlab platform.

  • BLIMP-1 and STAT3 Counterregulate MicroRNA-21 during Plasma Cell Differentiation
    The Journal of Immunology, 2012
    Co-Authors: N. A. Barnes, Matteo Cocco, R. M. Tooze, Sophie Stephenson, G M Doody
    Abstract:

    During Cellular Differentiation, mRNA transcription and translation require precise coordination. The mechanisms controlling this are not well defined. IL-21 is an important regulator of plasma Cell Differentiation, and it controls the master regulator of plasma Cell Differentiation, B lymphocyte-induced maturation protein-1 (BLIMP-1), via STAT3 and IRF4. Among the other targets of STAT3 is microRNA-21 (miR-21). miR-21 is the most frequently deregulated microRNA in malignancy, including B Cell lymphomas, and it has oncogenic potential downstream of STAT3. However, the regulation and function of miR-21 during plasma Cell Differentiation are not characterized. In contrast to the induction of miR-21 observed in response to STAT3 activation in other systems, we demonstrate that miR-21 is repressed during IL-21-driven plasma Cell Differentiation. We explored the molecular basis for this repression and identify primary miR-21 transcription as a direct target of BLIMP-1-dependent repression, despite continued STAT3 activation and phospho-STAT3 binding to the primary miR-21 promoter. Thus, STAT3 and BLIMP-1 constitute an incoherent feed-forward loop downstream of IL-21 that can coordinate microRNA with mRNA expression during plasma Cell Differentiation.

Hsia Yuan Ying - One of the best experts on this subject based on the ideXlab platform.

  • SUMOylation of Blimp-1 is critical for plasma Cell Differentiation
    EMBO Reports, 2012
    Co-Authors: Hsia Yuan Ying, Shin Tang Su, Pang Hung Hsu, Che Chang Chang, I. Ying Lin, Yu Hsuan Tseng, Hsiu Ming Shih, Ming-daw Tsai, Kuo-i Lin
    Abstract:

    Transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) is a master regulator of plasma Cell Differentiation. Here we show that Blimp-1 is covalently modified by SUMO1 at lysine 816, a modification mediated by SUMO E3 ligase PIAS1. Mutation of Blimp-1 lysine 816 reduces transcriptional repression--correlating with a reduced interaction with a histone deacetylase, HDAC2--and impairs Differentiation of antibody-secreting Cells. Thus, the SUMO pathway critically regulates Blimp-1 function during plasma Cell Differentiation.