Abstract：
:In the absence of IL-10, colonic inflammation ensues, which is characterized by high levels of IL-17. Here, we demonstrate a direct correlation between ICOS expression and IL-17 production in cIELs. IL-10(-/-) mice had increased numbers of cIELs and greater colon weight. Although the CD69 early activation antigen was expressed on cIELs from normal and IL-10(-/-) mice, ICOS was expressed only on cIELs from IL-10(-/-) mice. IL-17-producing cells in IL-10(-/-) mice consisted of CD4(+) and CD8(+) cIELs; however, CD4(+) cells were the predominant IL-17-producing cell population. Culture of cIELs from IL-10(-/-) mice with IL-23 resulted in an increase in ICOS and IL-17 expression, whereas IL-10 suppressed expression of ICOS and IL-17. This occurred in primary cultures and recall stimulation experiments. The ICOS ligand B7RP-1 was up-regulated on colonic epithelial cells and on a population of large granular leukocytes during inflammation. Culture of cIELs with B7RP-1(+) DCs enhanced IL-17A production from normal cIELs but failed to do so using cIELs from ICOS(-/-) mice. In vivo treatment of IL-10(-/-) mice with antibody to ICOS resulted in a significant reduction in colonic pathology. These findings implicate ICOS as an activational signal of Th17 cells during chronic intestinal inflammation, and they suggest that under some conditions, control of ICOS expression may help to suppress chronic intestinal inflammation.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Schaefer JS,Montufar-Solis D,Vigneswaran N,Klein JRdoi
10.1189/jlb.0409238subject
Has Abstractpub_date
2010-02-01 00:00:00pages
301-8issue
2eissn
0741-5400issn
1938-3673pii
jlb.0409238journal_volume
87pub_type
杂志文章abstract：:The transcription factor nuclear factor (NF)-kappaB controls the expression of genes involved in inflammation, cell proliferation, apoptosis, and differentiation. Impaired regulation of NF-kappaB has been associated with many diseases; thus, there is significant interest in therapeutic approaches based on modulation o...
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更新日期：2004-07-01 00:00:00
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journal_title：Journal of leukocyte biology
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doi：
更新日期：2001-06-01 00:00:00
