NKT Cell-Deficient Mice Harbor an Altered Microbiota That Fuels Intestinal Inflammation during Chemically Induced Colitis
NKT Cell-Deficient Mice Harbor an Altered Microbiota That Fuels Intestinal Inflammation during Chemically Induced Colitis
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DOI：
10.4049/jimmunol.1601410
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发表时间：
2016-12-01
影响因子：
4.4
通讯作者：
Mallevaey, Thierry
中科院分区：
文献类型：
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作者：
Selvanantham, Thirumahal;Lin, Qiaochu;Mallevaey, Thierry
NKT细胞是非常规的T细胞，其响应于自身和微生物来源的脂质和糖脂Ag由CD1d分子呈递。不变NKT（iNKT）细胞影响许多疾病的免疫反应。虽然只有少数研究已经检查了它们在肠道炎症中的作用，但似乎iNKT细胞保护免受Th1介导的炎症，但加剧Th2介导的炎症。使用iNKT细胞缺陷小鼠和化学诱导的葡聚糖硫酸钠（DSS）结肠炎的研究导致了不一致的结果。在这项研究中，我们发现，缺乏所有NKT细胞的CD1d缺陷小鼠，肠道微生物群发生了改变，这与稳态和DSS治疗后肠道炎症加剧有关。这种改变的微生物群的特征在于细菌门变形菌门、脱铁菌门和TM 7的丰度增加，其中包括吃粘蛋白的黏菌属以及普雷沃氏菌属和分节丝状细菌的成员，其在粪便移植后可传播，沿着原结肠表型。我们的研究结果还表明，这种促炎微生物群在DSS结肠炎期间激活后影响iNKT细胞功能。总的来说，微生物群的改变对结肠炎的结果有重大影响，因此必须在这样的实验环境和专注于iNKT细胞的研究中加以考虑。
NKT cells are unconventional T cells that respond to self and microbe-derived lipid and glycolipid Ags presented by the CD1d molecule. Invariant NKT (iNKT) cells influence immune responses in numerous diseases. Although only a few studies have examined their role during intestinal inflammation, it appears that iNKT cells protect from Th1-mediated inflammation but exacerbate Th2-mediated inflammation. Studies using iNKT cell deficient mice and chemically induced dextran sodium sulfate (DSS) colitis have led to inconsistent results. In this study, we show that CD1d-deficient mice, which lack all NKT cells, harbor an altered intestinal microbiota that is associated with exacerbated intestinal inflammation at steady-state and following DSS treatment. This altered microbiota, characterized by increased abundance of the bacterial phyla Proteobacteria, Deferribacteres, and TM7, among which the mucin-eating Mucispirillum, as well as members of the genus Prevotella and segmented filamentous bacteria, was transmissible upon fecal transplant, along with the procolitogenic phenotype. Our results also demonstrate that this proinflammatory micro biota influences iNKT cell function upon activation during DSS colitis. Collectively, alterations of the microbiota have a major influence on colitis outcome and therefore have to be accounted for in such experimental settings and in studies focusing on iNKT cells.