IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis

Ken Sugimoto, Atsuhiro Ogawa, Emiko Mizoguchi, Yasuyo Shimomura, Akira Andoh, Atul K. Bhan, Richard S. Blumberg, Ramnik J. Xavier, Atsushi Mizoguchi

研究成果: Article

629 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)534-544
ページ数11
ジャーナルJournal of Clinical Investigation
118
発行部数2
DOI
出版物ステータスPublished - 01-02-2008

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Ulcerative Colitis
Inflammation
Colitis
Mucus
Gene Transfer Techniques
Goblet Cells
Inflammatory Bowel Diseases
Intestines
Carrier Proteins
interleukin-22
Genes
Dextran Sulfate
Microinjections
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Medicine(all)

これを引用

Sugimoto, K., Ogawa, A., Mizoguchi, E., Shimomura, Y., Andoh, A., Bhan, A. K., ... Mizoguchi, A. (2008). IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. Journal of Clinical Investigation, 118(2), 534-544. https://doi.org/10.1172/JCI33194
Sugimoto, Ken ; Ogawa, Atsuhiro ; Mizoguchi, Emiko ; Shimomura, Yasuyo ; Andoh, Akira ; Bhan, Atul K. ; Blumberg, Richard S. ; Xavier, Ramnik J. ; Mizoguchi, Atsushi. / IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. :: Journal of Clinical Investigation. 2008 ; 巻 118, 番号 2. pp. 534-544.
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abstract = "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.",
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Sugimoto, K, Ogawa, A, Mizoguchi, E, Shimomura, Y, Andoh, A, Bhan, AK, Blumberg, RS, Xavier, RJ & Mizoguchi, A 2008, 'IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis', Journal of Clinical Investigation, 巻. 118, 番号 2, pp. 534-544. https://doi.org/10.1172/JCI33194

IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. / Sugimoto, Ken; Ogawa, Atsuhiro; Mizoguchi, Emiko; Shimomura, Yasuyo; Andoh, Akira; Bhan, Atul K.; Blumberg, Richard S.; Xavier, Ramnik J.; Mizoguchi, Atsushi.

:: Journal of Clinical Investigation, 巻 118, 番号 2, 01.02.2008, p. 534-544.

研究成果: Article

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T1 - IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis

AU - Sugimoto, Ken

AU - Ogawa, Atsuhiro

AU - Mizoguchi, Emiko

AU - Shimomura, Yasuyo

AU - Andoh, Akira

AU - Bhan, Atul K.

AU - Blumberg, Richard S.

AU - Xavier, Ramnik J.

AU - Mizoguchi, Atsushi

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N2 - 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.

AB - 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.

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