研究者業績

下村 泰代

shimomura yasuyo

基本情報

所属
藤田医科大学 医学部 医学科 麻酔・侵襲制御医学 講師
学位
博士(医学)

J-GLOBAL ID
201501014846386170
researchmap会員ID
7000012991

論文

 8
  • Yasuyo Shimomura, Emiko Mizoguchi, Ken Sugimoto, Ryoko Kibe, Yoshimi Benno, Atsushi Mizoguchi, Atul K. Bhan
    INTERNATIONAL IMMUNOLOGY 20(6) 729-737 2008年6月  査読有り
    According to the 'hygiene hypothesis', enhanced microbial exposure due to early childhood infections leads to a reduction of T(h)2-mediated allergic diseases and inflammatory bowel disease. To begin to elucidate the mechanisms underlying this hypothesis, we studied development of T(h)2-mediated colitis of the TCR alpha knockout (KO) mouse in both a specific pathogen-free (SPF) facility and a conventional (CV) facility. After more than five generations in each facility, TCR alpha KO mice kept in the CV facility developed dramatically less colitis than mice that were kept in the SPF facility. Surprisingly, the suppression of colitis in the CV facility correlated with a significant increase in natural IgM production by B-1 B cells. In contrast, B cell-deficient TCR alpha double-knockout (alpha mu DKO) mice maintained in the CV facility continued to develop severe colitis, strongly suggesting that B-1 B cells contributed to the suppression of colitis. Indeed, the adoptive transfer of B-1 B cells isolated from the peritoneal cavity of TCR alpha KO mice (SPF) into alpha mu DKO mice (CV) suppressed the development of colitis in the recipient mice. We conclude that B-1 cells play a regulatory role in T(h)2-mediated colitis under non-hygienic conditions, possibly by generating natural antibodies in response to microbial flora.
  • Yasuyo Shimomura, Atsuhiro Ogawa, Mayumi Kawada, Ken Sugimoto, Emiko Mizoguchi, Hai-Ning Shi, Shiv Pillai, Atul K. Bhan, Atsushi Mizoguchi
    JOURNAL OF EXPERIMENTAL MEDICINE 205(6) 1343-1355 2008年6月  査読有り
    Over 80% of the body's activated B cells are located in mucosal sites, including the intestine. The intestine contains IgM(+) B cells, but these cells have not been characterized phenotypically or in terms of their developmental origins. We describe a previously unidentified and unique subset of immunoglobulin M+ B cells that present with an AA4.1(-)CD21(-)CD23(-) major histocompatibility complex class IIbright surface phenotype and are characterized by a low frequency of somatic hypermutation and the potential ability to produce interleukin-12p70. This B cell subset resides within the normal mucosa of the large intestine and expands in response to inflammation. Some of these intestinal B cells originate from the AA4.1(+) immature B2 cell pool in the steady state and are also recruited from the recirculating naive B cell pool in the context of intestinal inflammation. They develop in an antigen-independent and BAFF-dependent manner in the absence of T cell help. Expansion of these cells can be induced in the absence of the spleen and gut-associated lymphoid tissues. These results describe the existence of an alternative pathway of B cell maturation in the periphery that gives rise to a tissue-specific B cell subset.
  • Kiyotaka Nagahama, Atsuhiro Ogawa, Katsunori Shirane, Yasuko Shimomura, Ken Sugimoto, Atsushi Mizoguchi
    GASTROENTEROLOGY 134(2) 459-469 2008年2月  査読有り
    Background & Aims: Dysregulated host/microbial interactions induce the development of colitis by activating deleterious acquired immune responses. Activation of CD4(+) T cells is mainly induced through signaling machinery associated with immunologic synapse (IS). A key molecule associated with the IS is protein kinase C (PKC) theta. However, the role of PKC theta in the pathogenesis of colitis has not fully been defined. Methods: The role of PKC theta for the acquired-immune responses involved in the development of different types of colitis (CD45RB model, T-cell receptor [TCR] alpha knockout [KO] mice and interleukin [IL]-2KO mice) was examined by generating double KO mice and by utilizing cell transfer approaches. Results: Adoptive transfer of PKC theta-deficient naive CD4+ T cells failed to induce T helper cell (Th) 1-mediated colitis in the immune-deficient host (CD45RB model). Development of Th2-mediated colitis in TCR alpha KO mice was also inhibited by the absence of PKC theta. In IL-2KO mice, which develop colitis because of dysregulated T-cell homeostasis, deficiency of PKC theta in CD4(+) T cells failed to induce the development of severe colitis. Interestingly, absence of PKC theta led to a remarkable decrease in the proliferation, but not apoptosis, of colonic memory CD4(+) T cells. This impaired proliferation resulted in a marked decrease in the colonic CD4(+) T cells that are capable of producing IL-17. In addition, deficiency of PKC theta inhibited the production of Th2 cytokines by colonic CD4(+) T cells. Conclusions: PKC theta serves as a common and fundamental signaling molecule in the development of different types of colitis and may represent an attractive target for treating inflammatory bowel disease.
  • Ken Sugimoto, Atsuhiro Ogawa, Emiko Mizoguchi, Yasuyo Shimomura, Akira Andoh, Atul K. Bhan, Richard S. Blumberg, Ramnik J. Xavier, Atsushi Mizoguchi
    JOURNAL OF CLINICAL INVESTIGATION 118(2) 534-544 2008年2月  査読有り
    Expression of IL-22 is induced in several human inflammatory conditions, including inflammatory bowel disease (IBD). Expression of the IL-22 receptor is restricted to innate immune cells; however, the role of IL-22 in colitis has not yet been defined. We developed what we believe to be a novel microinjection-based local gene-delivery system that is capable of targeting the inflamed intestine. Using this approach, we demonstrated a therapeutic potency for IL-22-mediated activation of the innate immune pathway in a mouse model of Th2-mediated colitis that induces disease with characteristics similar to that of IBD ulcerative colitis (UC). IL-22 gene delivery enhanced STAT3 activation specifically within colonic epithelial cells and induced both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. Importantly, IL-22 gene delivery led to rapid amelioration of local intestinal inflammation. The amelioration of disease by IL-22 was mediated by enhanced mucus production. In addition, local gene delivery was used to inhibit IL-22 activity through overexpression of IL-22-binding protein. Treatment with IL-22-binding protein suppressed goblet cell restitution during the recovery phase of a dextran sulfate sodium-induced model of acute colitis. These data demonstrate what we believe to be a novel function for IL-22 in the intestine and suggest the potency of a local IL-22 gene-delivery system for treating UC.
  • Masanobu Nanno, Yasuyoshi Kanari, Tomoaki Naito, Nagamu Inoue, Tadakazu Hisamatsu, Hiroshi Chinen, Ken Sugimoto, Yasuyo Shimomura, Hideo Yamagishi, Tetsuo Shiohara, Satoshi Ueha, Kouji Matsushima, Makoto Suematsu, Atsushi Mizoguchi, Toshifumi Hibi, Atul K. Bhan, Hiromichi Ishikawa
    GASTROENTEROLOGY 134(2) 481-490 2008年2月  査読有り
    Background & Aim: T-cell receptor (TCR) gamma delta T cells are an important component of the mucosal immune system and regulate intestinal epithelial homeostasis. Interestingly, there is a significant increase in gamma delta T cells in the inflamed mucosa of patients with ulcerative colitis (UC). However, the role of gamma delta T cells in chronic colitis has not been fully identified. Methods: TCR alpha-deficient mice, which spontaneously develop chronic colitis with many features of human UC including an increase in gamma delta T-cell population, represent an excellent model to investigate the role of gamma delta T cells in UC-like colitis. To identify the role of gamma delta T cells in this colitis, we herein have generated TCR gamma-deficient mice through deletion of all TCR C gamma genes (C gamma 1, C gamma 2, C gamma 3, and C gamma 4) using the Cre/loxP site-specific recombination system and subsequently crossing these mice with TCR alpha-deficient mice. Results: An increase in colonic gamma delta T cells was associated with the development of human UC as well as UC-like disease seen in TCR alpha-deficient mice. Interestingly, the newly established TCR alpha(-/-) x TCR gamma(-/-) double mutant mice developed significantly less severe colitis as compared with TCR alpha-deficient mice. The suppression of colitis in TCR alpha(-/-) x TCR gamma(-/-) double mutant mice was associated with a significant reduction of proinflammatory cytokine and chemokine productions and a decrease in neutrophil infiltration. Conclusions: gamma delta T cells are involved in the exacerbation of UC-like chronic disease. Therefore, gamma delta T cells may represent a promising therapeutic target for the treatment of human UC.

MISC

 10
  • 西田 修, 湯本美穂, 森山和広, 加藤由布, 下村泰代, 中村智之, 栗山直英, 原 嘉孝, 伊藤 舞, 野田昌宏, 秋山正慶, 早川聖子, 小松聖史, 山田晋吾, 宮庄 拓
    日本アフェレイシス学会雑誌 31(2) 148-155 2012年  
  • 山下千鶴, 西田 修, 伊藤 舞, 中村智之, 栗山直英, 原 嘉孝, 柴田純平, 下村泰代, 安岡なつみ, 河田耕太郎, 内山壮太, 栃井都紀子, 湯本美穂, 山田晋吾, 宮庄 拓
    エンドトキシン血症救命治療研究会誌 16(1) 172-177 2012年  
  • Miho Yumoto, Osamu Nishida, Kazuhiro Moriyama, Yasuyo Shimomura, Tomoyuki Nakamura, Naohide Kuriyama, Yoshitaka Hara, Shingo Yamada
    THERAPEUTIC APHERESIS AND DIALYSIS 15(4) 385-393 2011年8月  
    The high mobility group box 1 protein (HMGB1) is an alarmin that plays an important role in sepsis and has been recognized as a promising target with a wide therapeutic window; however, no drugs and devices are currently in practical use. We hypothesized that hemofilters composed of porous membranes or cytokine-adsorbing membranes could remove HMGB1 from the blood. We performed experimental hemofiltration in vitro using four types of hemofilters composed of different membranes specifically designed for continuous hemofiltration. The test solution was a 1000-mL substitution fluid containing 100 mu g of HMGB1 and 35 g of bovine serum albumin. Experimental hemofiltration was conducted for 360 min in a closed loop circulation system. Among the four membranes, surface-treated polyacrylonitrile (AN69ST) showed the highest capacity to adsorb HMGB1; it adsorbed nearly 100 mu g of HMGB1 in the initial 60 min and showed a markedly high clearance rate (60.8 +/- 5.0 mL/min) at 15 min. The polymethylmethacrylate membrane had half of the adsorption capacity of the AN69ST membrane. Although the highest sieving coefficient for HMGB1 was obtained with the high cut-off polyarylethersulfone membrane, which correlated with a constant filtrate clearance rate, albumin loss was observed. However, no such removal of both HMGB1 and albumin was observed with the polysulfone membrane and tubing. We conclude that continuous hemofiltration using the AN69ST membrane is a promising approach for HMGB1-related sepsis.
  • 栗山直英, 西田 修, 原 嘉孝, 中村智之, 湯本美穂, 柴田純平, 山下千鶴, 下村泰代, 安岡なつみ, 早川聖子, 栃井都紀子, 伊藤 舞, 内山壮太, 河田耕太郎, 野田昌宏, 秋山正慶, 須賀美華, 森 志乃
    バイオメディカル 21 4-8 2011年  
    ICU入室時のThrombin-antithrombin complex(TAT)値および乳酸値と、SOFAスコア、APACHE IIスコアとICU室期間との関連を調べ、重症度の判定や予後予測の指標になり得るか検討した。ICUに3日間以上滞在し、28日間以内に退室した連続30例を対象とした。入室期間が7日間未満(A群)と7日間以上(B群)で2群に分けた。ICU入室時のTAT値とSOFAスコアは正の相関関係を示し、ICU入室時のTATとAPACHE IIスコアも正の相関関係を示した。TAT値はB群で有意に高かった。血清乳酸値もB群で有意に高かった。また、SOFAスコアはB群で有意に高く、APACHE IIスコアもB群で有意に高かった。
  • 湯本美穂, 西田 修, 森山和広, 下村泰代, 中村智之, 栗山直英, 原 嘉孝, 宮庄 拓, 山田晋吾
    日本急性血液浄化学会雑誌 2(1) 97-103 2011年  
  • 西田 修, 中村智之, 湯本美穂, 栗山直英, 原 嘉孝, 下村泰代, 山下千鶴, 柴田純平
    体液・代謝管理 27 21-31 2011年  
  • Nishida O, Nakamura T, Kuriyama N, Hara Y, Yumoto M, Shimomura Y, Moriyama K
    Contrib Nephrol 173 172-181 2011年  
  • 栗山直英, 西田 修, 伊藤 舞, 内山壮太, 河田耕太郎, 栃井都紀子, 早川聖子, 安岡なつみ, 原 嘉孝, 森山和広, 中村智之, 下村泰代, 湯本美穂
    臨床麻酔 34(3) 581-587 2010年  
  • 西田 修, 栗山直英, 中村智之, 下村泰代, 湯本美穂
    救急・集中治療 7,8月号 21 920-928 2009年  
  • 西田 修, 中村智之, 湯本美穂, 下村泰代, 栗山直英
    救急・集中治療 11,12月号 21 1651-1660 2009年  

書籍等出版物

 7

講演・口頭発表等

 104