日本語フィールド
著者：Hidekazu Itamura, Takero Shindo, Hiroyuki Muranushi, Kazutaka Kitaura, Seiji Okada, Tadasu Shin-I , Ryuji Suzuki, Akifumi Takaori-Kondo, Shinya Kimura題名：Pharmacological MEK inhibition promotes polyclonal T-cell reconstitution and suppresses xenogeneic GVHD 発表情報：Cell Immunol 巻: 367 ページ: 104410キーワード：Graft-versus-host disease; Hematopoietic cell transplantation; Immune reconstitution; MEK inhibitor; T-cell receptor (TCR) repertoire概要：Rapid immune reconstitution without developing graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation. Here, we analyzed the effects of pharmacological MEK inhibition on human polyclonal T-cell reconstitution in a humanized mouse GVHD model utilizing deep sequencing-based T-cell receptor (TCR) repertoire analysis. GVHD mice exhibited a skewed TCR repertoire with a common clone within target organs. The MEK inhibitor trametinib ameliorated GVHD and enabled engraftment of diverse T-cell clones. Furthermore, trametinib also ameliorated GVHD sparing diverse T cell repertoire, even when it was given from day 15 through 28. Although tacrolimus also reduced development of GVHD, it disturbed diverse T cell reconstitution and resulted in skewed TCR repertoire. Thus, trametinib not only suppresses GVHD-inducing T cells but also promotes human T cell reconstitution in vivo, providing a novel rationale for translational studies targeting human GVHD. 抄録：英語フィールド
Author：Hidekazu Itamura, Takero Shindo, Hiroyuki Muranushi, Kazutaka Kitaura, Seiji Okada, Tadasu Shin-I , Ryuji Suzuki, Akifumi Takaori-Kondo, Shinya KimuraTitle：Pharmacological MEK inhibition promotes polyclonal T-cell reconstitution and suppresses xenogeneic GVHD Announcement information:Cell Immunol Vol: 367 Page: 104410Keyword：Graft-versus-host disease; Hematopoietic cell transplantation; Immune reconstitution; MEK inhibitor; T-cell receptor (TCR) repertoireAn abstract：Rapid immune reconstitution without developing graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation. Here, we analyzed the effects of pharmacological MEK inhibition on human polyclonal T-cell reconstitution in a humanized mouse GVHD model utilizing deep sequencing-based T-cell receptor (TCR) repertoire analysis. GVHD mice exhibited a skewed TCR repertoire with a common clone within target organs. The MEK inhibitor trametinib ameliorated GVHD and enabled engraftment of diverse T-cell clones. Furthermore, trametinib also ameliorated GVHD sparing diverse T cell repertoire, even when it was given from day 15 through 28. Although tacrolimus also reduced development of GVHD, it disturbed diverse T cell reconstitution and resulted in skewed TCR repertoire. Thus, trametinib not only suppresses GVHD-inducing T cells but also promotes human T cell reconstitution in vivo, providing a novel rationale for translational studies targeting human GVHD. 