Defect in CEACAM family member expression in Crohn's disease IECs is regulated by the transcription factor SOX9.
Defect in CEACAM family member expression in Crohn's disease IECs is regulated by the transcription factor SOX9.
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DOI：
10.1002/ibd.21023
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发表时间：
2009-12
影响因子：
4.9
通讯作者：
Mayer, Lloyd
中科院分区：
文献类型：
--
作者：
Roda, Giulia;Dahan, Stephanie;Mezzanotte, Laura;Caponi, Alessandra;Roth-Walter, Franziska;Pinn, David;Mayer, Lloyd
CEACAM1、CEACAM5和CEACAM6是表达于肠上皮细胞的CEACAM亚家族中的三个成员。在炎症性肠病(IBD)中，它们的表达不足会导致粘膜中CD8+调节性T细胞缺乏激活。由于CEACAM的表达受转录因子SOX9的调节，我们试图确定在IBD中CEACAM的表达缺陷是否与SOX9的异常表达有关。新鲜分离IECs和固有层淋巴细胞(LPLs)。T84和HT29 16E细胞与LPLs共培养。用实时定量聚合酶链式反应、Western Blot、免疫组织化学和免疫荧光法检测SOX9和CEACAM亚家族成员的表达。在克罗恩病(CD)中，CEACAM1和CEACA5的mRNA和蛋白表达均显著降低，而SOX9的表达则无明显差异。而在CD IECS中，SOX9的核表达增强。此外，LPL刺激的T84和HT29 16E细胞胞浆中SOX9蛋白表达减少，CEACAM5表达增加。CDIECS中CEACAM家族成员的缺陷可能与SOX9的核定位异常有关。CD粘膜SOX9表达的变化与局部微环境和IEC：LPL串扰改变有关。
CEACAM1, CEACAM5 and CEACAM6 represent three of the CEACAM subfamily members expressed on intestinal epithelial cells (IECs). Deficiency in their expression, as seen in inflammatory bowel disease (IBD), results in the lack of activation of CD8+ regulatory T cells in the mucosa. Since CEACAM expression was shown to be regulated by the transcription factor SOX9, we sought to determine whether the defect in CEACAM expression in IBD was related to aberrant SOX9 expression. IECs and lamina propria lymphocytes (LPLs) were freshly isolated from colonic tissues. T84 and HT29 16E cells were co-cultured with LPLs. SOX9 and CEACAM subfamily member expression was assessed by Real-Time PCR, Western Blot, immunohistochemistry and immunofluorescence. In Crohn’s disease (CD) but not in ulcerative colitis (UC), a significant reduction in mRNA and protein expression for CEACAM1 and 5 was noted, in contrast, no difference in SOX9 mRNA expression was seen. However, nuclear SOX9 immunostaining was increased in CD IECs. Furthermore, SOX9 protein was reduced in the cytoplasm of LPL stimulated- T84 and HT29 16E cells, while CEACAM5 expression was increased. The defect in CEACAM family members in CD IECs appears to be related to the aberrant nuclear localization of SOX9. Changes in SOX9 expression in the CD mucosa relate to local microenvironment and altered IEC:LPL crosstalk.
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DOI：
10.1084/jem.166.5.1471
发表时间：
1987-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mayer L;Shlien R
通讯作者：
Shlien R
DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blache P;van de Wetering M;Duluc I;Domon C;Berta P;Freund JN;Clevers H;Jay P
通讯作者：
Jay P
影响因子：
4.8
作者：
Campbell, NA;Kim, HS;Mayer, L
通讯作者：
Mayer, L
影响因子：
15.3
作者：
LI, Y;YIO, XY;MAYER, L
通讯作者：
MAYER, L
影响因子：
3.9
作者：
Soullier, S;Jay, P;Laudet, V
通讯作者：
Laudet, V