Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease.
Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease.
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DOI：
10.3389/fimmu.2018.02475
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发表时间：
2018
影响因子：
7.3
通讯作者：
Sisirak V
中科院分区：
文献类型：
--
作者：
Sawai CM;Serpas L;Neto AG;Jang G;Rashidfarrokhi A;Kolbeck R;Sanjuan MA;Reizis B;Sisirak V
炎症性肠病（IBD）是一种慢性炎症性疾病，由对胃肠道微生物成分的异常免疫反应引起。浆细胞样树突状细胞（Plasmacytoid dendritic cells，pDC）是一种特异性产生I型干扰素的先天性免疫细胞，最近被发现与狼疮和硬皮病等自身免疫性疾病的发病机制有关。虽然pDC显示浸润IBD患者的肠粘膜，并提出参与肠道炎症，但其对疾病的净贡献仍不清楚。我们通过靶向由Wiskott-Aldrich综合征蛋白（WASP）或白细胞介素-10（IL-10）缺乏引起的实验性IBD中的pDC特异性转录因子TCF 4（E2-2）来解决这个问题。单等位基因Tcf 4缺失，这是以前被证明废除实验性狼疮，不影响自身免疫表现或结肠炎WASP缺陷动物。此外，条件性双等位基因Tcf 4靶向导致接近完全的pDC消融，但对IL-10缺陷小鼠中结肠炎的发展没有影响。我们的研究结果表明，与其他炎症和自身免疫性疾病相比，pDC在IBD期间的肠道炎症发病机制中不起主要作用。
Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicated in the pathogenesis of autoimmune disorders such as lupus and scleroderma. While pDCs were shown to infiltrate intestinal mucosa of IBD patients and proposed to participate in intestinal inflammation, their net contribution to the disease remains unclear. We addressed this question by targeting the pDC-specific transcription factor TCF4 (E2-2) in experimental IBD caused by deficiency of Wiskott-Aldrich syndrome protein (WASP) or of interleukin-10 (IL-10). Monoallelic Tcf4 deletion, which was previously shown to abrogate experimental lupus, did not affect autoimmunity manifestations or colitis in WASP-deficient animals. Furthermore, conditional biallelic Tcf4 targeting resulted in a near-complete pDC ablation, yet had no effect on the development of colitis in IL-10-deficient mice. Our results suggest that, in contrast to other inflammatory and autoimmune diseases, pDCs do not play a major role in the pathogenesis of intestinal inflammation during IBD.
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影响因子：
32.4
作者：
Goubier, Anne;Dubois, Bertrand;Gheit, Hanane;Joubert, Grgoire;Villard-Truc, Florence;Asselin-Paturel, Carine;Trinchieri, Giorgio;Kaiserlian, Dominique
通讯作者：
Kaiserlian, Dominique
DOI：
10.1084/jem.20062648
发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Caton ML;Smith-Raska MR;Reizis B
通讯作者：
Reizis B
影响因子：
20.3
作者：
Hao, Yi;O'Neill, Patrick;Cancro, Michael P.
通讯作者：
Cancro, Michael P.
影响因子：
8.2
作者：
Hannibal TD;Schmidt-Christensen A;Nilsson J;Fransén-Pettersson N;Hansen L;Holmberg D
通讯作者：
Holmberg D
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V