Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation.
Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation.
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DOI：
10.1084/jem.20160062
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发表时间：
2016-04-04
期刊：
影响因子：
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通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
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作者：
Loschko J;Schreiber HA;Rieke GJ;Esterházy D;Meredith MM;Pedicord VA;Yao KH;Caballero S;Pamer EG;Mucida D;Nussenzweig MC
Nussenzweig等人使用了一种在常规树突状细胞（cDC）上缺乏MHC II类表达的新型突变小鼠，以证明cDC在维持肠道稳态中的重要性。传统的树突状细胞（cDC）通过启动适应性T细胞应答和作为先天免疫传感器在宿主免疫中发挥重要作用。虽然cDC的先天和适应性功能都有很好的记录，但它们在维持免疫稳态中的相对重要性知之甚少。为了研究cDC启动的适应性免疫在维持稳态中的意义，独立于其先天活性，我们产生了cDC特异性Cre小鼠并将其与floxed MHC II类（MHCII）小鼠杂交。cDC上MHCII的缺乏导致慢性肠道炎症，其通过抗生素治疗减轻，并且在无菌条件下完全避免。cDC的先天和适应性功能的解偶联揭示了cDC的先天免疫功能不足以维持稳态，并且cDC的抗原呈递对于宿主和肠道细菌之间的互利关系是必不可少的。
Nussenzweig et al. use a novel mutant mouse lacking MHC class II expression on conventional dendritic cells (cDCs) to demonstrate the importance of cDCs in the maintenance of intestinal homeostasis. Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative importance in maintaining immune homeostasis is poorly understood. To examine the significance of cDC-initiated adaptive immunity in maintaining homeostasis, independent of their innate activities, we generated a cDC-specific Cre mouse and crossed it to a floxed MHC class II (MHCII) mouse. Absence of MHCII on cDCs resulted in chronic intestinal inflammation that was alleviated by antibiotic treatment and entirely averted under germ-free conditions. Uncoupling innate and adaptive functions of cDCs revealed that innate immune functions of cDCs are insufficient to maintain homeostasis and antigen presentation by cDCs is essential for a mutualistic relationship between the host and intestinal bacteria.