Commensal bacteria exacerbate intestinal inflammation but are not essential for the development of murine ileitis
Commensal bacteria exacerbate intestinal inflammation but are not essential for the development of murine ileitis
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DOI：
10.4049/jimmunol.178.3.1809
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Cominelli, Fabio
中科院分区：
文献类型：
--
作者：
Bamias, Giorgos;Okazawa, Akira;Cominelli, Fabio
克罗恩病的发病机制与粘膜免疫系统针对细菌来源的腔内抗原的失调反应有关。在这项研究中，我们研究了无菌 (GF) 条件对克罗恩病样回肠炎 SANW1/YitFc 小鼠模型的影响。我们证明细菌菌群对于诱导回肠炎不是必需的，因为 GF SAMEP1/YitFc 小鼠会发展为慢性回肠炎。然而，与无特定病原体（SPF）小鼠的疾病相比，GF小鼠的回肠炎明显减弱，并且与淋巴细胞浸润延迟和Th2细胞因子的粘膜表达缺陷有关。此外，我们证明用 SPF 小鼠（而非 GF 小鼠）纯化的粪便 Ag 进行刺激会导致分泌 IL-4 的效应淋巴细胞的产生。这一结果表明，共生细菌驱动 SAMP1/YitFe 回肠炎慢性期特征的 Th2 反应。最后，从 GF 小鼠（而非 SPF 小鼠）过继转移 CD4 阳性细胞会在 SCID 受体中诱发严重结肠炎。与SPF小鼠相比，这些效应与GF小鼠肠系膜淋巴结中CD4(+)CD25(+)Foxp3(+)T细胞频率降低以及GF小鼠CD4(+)CD25(+)T细胞中Foxp3相对基因表达降低有关。由此可见，在.如果腔内没有活细菌，粘膜免疫系统的调节部分就会受到损害。总而言之，我们的结果表明，在 SAiMP1/YitFc 小鼠中，细菌菌群会加剧肠道炎症，但对于这些小鼠特有的慢性回肠炎的产生并不是必需的。
The pathogenesis of Crohn's disease has been associated with a dysregulated response of the mucosal immune system against intraluminal Ags of bacterial origin. In this study, we have investigated the effects of germfree (GF) conditions in the SANW1/YitFc murine model of Crohn's disease-like ileitis. We show that the bacterial flora is not essential for ileitis induction, because GF SAMEP1/YitFc mice develop chronic ileitis. However, compared with disease in specific pathogen-free (SPF) mice, ileitis in GF mice is significantly attenuated, and is associated with delayed lymphocytic infiltration and defective mucosal expression of Th2 cytokines. In addition, we demonstrate that stimulation with purified fecal Ags from SPF, but not GF mice leads to the generation of IL-4-secreting effector lymphocytes. This result suggests that commensal bacteria drive Th2 responses characteristic of the chronic phase of SAMP1/YitFe ileitis. Finally, adoptive transfer of CD4-positive cells from GF, but not SPF mice induces severe colitis in SCID recipients. These effects were associated with a decreased frequency of CD4(+)CD25(+)Foxp3(+) T cells in the mesenteric lymph nodes of GF mice compared with SPF mice, as well as lower relative gene expression of Foxp3 in CD4(+)CD25(+) T cells in GF mice. It is therefore apparent that, in the. absence of live intraluminal bacteria, the regulatory component of the mucosal immune system is compromised. All together, our results indicate that in SAiMP1/YitFc mice, bacterial flora exacerbates intestinal inflammation, but is not essential for the generation of the chronic ileitis that is characteristic of these mice.