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Clinical importance of IL-22 cascade in IBD

IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct differe...

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Autores principales: Mizoguchi, Atsushi, Yano, Arisa, Himuro, Hidetomo, Ezaki, Yui, Sadanaga, Takayuki, Mizoguchi, Emiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Japan 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866830/
https://www.ncbi.nlm.nih.gov/pubmed/29075900
http://dx.doi.org/10.1007/s00535-017-1401-7
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author Mizoguchi, Atsushi
Yano, Arisa
Himuro, Hidetomo
Ezaki, Yui
Sadanaga, Takayuki
Mizoguchi, Emiko
author_facet Mizoguchi, Atsushi
Yano, Arisa
Himuro, Hidetomo
Ezaki, Yui
Sadanaga, Takayuki
Mizoguchi, Emiko
author_sort Mizoguchi, Atsushi
collection PubMed
description IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct difference between large and small intestines. IL-22 possesses an ability to constitutively activate STAT3 for promoting epithelial cell regeneration and reinforcing mucosal barrier integrity through stimulating the expression of anti-bacterial peptide and mucins. Of note, IL-22 is characterized as a two-faced cytokine that can play not only protective but also deleterious roles in the intestinal inflammation depending on the cytokine environment such as the expression levels of IL-23, T-bet, and IL-22 binding protein. Most importantly, clinical relevance of IL-22 to inflammatory bowel disease has been well highlighted. Mucosal healing, which represents the current therapeutic goal for IBD, can be induced by IL-22. Indeed, indigo naturalis, which can activate IL-22 pathway through Ahr, has been shown in a clinical trial to exhibit a strong therapeutic effect on ulcerative colitis. Despite the beneficial effect of IL-22, continuous activation of the IL-22 pathway increases the risk of colitis-associated cancer, particularly in patients with an extended history of IBD. This review article discusses how IL-22 regulates colitis, how beneficial versus deleterious effects of IL-22 is determined, and why IL-22 represents a promising target for IBD therapy.
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spelling pubmed-58668302018-03-27 Clinical importance of IL-22 cascade in IBD Mizoguchi, Atsushi Yano, Arisa Himuro, Hidetomo Ezaki, Yui Sadanaga, Takayuki Mizoguchi, Emiko J Gastroenterol Review IL-22 is a relatively new cytokine that is characterized by several unique biological properties. In the intestines, the effect of IL-22 is restricted mainly to non-lymphoid cells such as epithelial cells. Interestingly, the expression pattern and major cellular source of IL-22 have distinct difference between large and small intestines. IL-22 possesses an ability to constitutively activate STAT3 for promoting epithelial cell regeneration and reinforcing mucosal barrier integrity through stimulating the expression of anti-bacterial peptide and mucins. Of note, IL-22 is characterized as a two-faced cytokine that can play not only protective but also deleterious roles in the intestinal inflammation depending on the cytokine environment such as the expression levels of IL-23, T-bet, and IL-22 binding protein. Most importantly, clinical relevance of IL-22 to inflammatory bowel disease has been well highlighted. Mucosal healing, which represents the current therapeutic goal for IBD, can be induced by IL-22. Indeed, indigo naturalis, which can activate IL-22 pathway through Ahr, has been shown in a clinical trial to exhibit a strong therapeutic effect on ulcerative colitis. Despite the beneficial effect of IL-22, continuous activation of the IL-22 pathway increases the risk of colitis-associated cancer, particularly in patients with an extended history of IBD. This review article discusses how IL-22 regulates colitis, how beneficial versus deleterious effects of IL-22 is determined, and why IL-22 represents a promising target for IBD therapy. Springer Japan 2017-10-26 2018 /pmc/articles/PMC5866830/ /pubmed/29075900 http://dx.doi.org/10.1007/s00535-017-1401-7 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Mizoguchi, Atsushi
Yano, Arisa
Himuro, Hidetomo
Ezaki, Yui
Sadanaga, Takayuki
Mizoguchi, Emiko
Clinical importance of IL-22 cascade in IBD
title Clinical importance of IL-22 cascade in IBD
title_full Clinical importance of IL-22 cascade in IBD
title_fullStr Clinical importance of IL-22 cascade in IBD
title_full_unstemmed Clinical importance of IL-22 cascade in IBD
title_short Clinical importance of IL-22 cascade in IBD
title_sort clinical importance of il-22 cascade in ibd
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866830/
https://www.ncbi.nlm.nih.gov/pubmed/29075900
http://dx.doi.org/10.1007/s00535-017-1401-7
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