Abstract:
BACKGROUND:Abrogating tolerance is a critical step in the pathogenesis of Crohn's disease (CD). T cell-anergy is one of the main mechanisms of tolerance and is regulated by the gene related to anergy in lymphocytes (GRAIL). This study investigated the expressions and regulation of GRAIL in CD and murine colitis models. METHODS:Expressions of GRAIL mRNA and protein in CD4+ T cells were investigated in the peripheral blood and mucosal tissues of patients with CD, mice with dextran sodium salt (DSS)-induced colitis, and Il-10-deficient mice. MicroRNAs responsible for the regulation of GRAIL were examined by miRNA microarray. GRAIL-overexpressing T cells were intravenously injected in mice with DSS-induced colitis. RESULTS:The GRAIL expression was higher in the lamina propria (LP) CD4+ T cells of CD patients than of the control subjects, while it was lower in the peripheral blood CD4+ T cells of the CD patients than of the control subjects. The GRAIL mRNA expression was lower, but the GRAIL protein expression was higher in the LP of colitic mice than that of non-colitic mice. The miRNA microarray identified miR-290-5p as an miRNA that inhibits expression of the GRAIL protein and that is highly expressed in the LP of non-colitic mice. GRAIL-expressing T cells expressed regulatory T cell markers and showed suppressive effects in murine DSS-induced colitis. CONCLUSIONS:Our results show that expression of GRAIL is uniquely regulated by the specific miRNA in the intestinal mucosa, and suggest that GRAIL may associate with the pathophysiology of CD.
journal_name
J Gastroenteroljournal_title
Journal of gastroenterologyauthors
Mukai A,Iijima H,Hiyama S,Fujii H,Shinzaki S,Inoue T,Shiraishi E,Kawai S,Araki M,Hayashi Y,Kondo J,Mizushima T,Kanto T,Egawa S,Nishida T,Tsujii M,Takehara Tdoi
10.1007/s00535-013-0923-xsubject
Has Abstractpub_date
2014-12-01 00:00:00pages
1524-35issue
12eissn
0944-1174issn
1435-5922journal_volume
49pub_type
杂志文章abstract::Prevention of human diseases has become a major focus of biomedical investigators around the world. Our current screening and treatment regimens for colorectal cancer are not effective, as indicated by the fact that this disease is the second leading cause of death from cancer in the United States. Recently published ...
journal_title:Journal of gastroenterology
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pub_type: 临床试验,杂志文章,随机对照试验
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