Expression of interleukin-10 in intestinal lymphocytes detected by an interleukin-10 reporter knockin tiger mouse
Expression of interleukin-10 in intestinal lymphocytes detected by an interleukin-10 reporter knockin tiger mouse
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DOI：
10.1016/j.immuni.2006.09.013
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发表时间：
2006-12-01
期刊：
影响因子：
32.4
通讯作者：
Flavell, Richard A.
中科院分区：
文献类型：
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作者：
Kamanaka, Masahito;Kim, Sean T.;Flavell, Richard A.
为了在体内鉴定产生白细胞介素 - 10（IL - 10）的细胞，我们构建了一种基因敲入小鼠，在IL - 10基因的多聚腺苷酸化位点之前直接插入了一个内部核糖体进入位点（IRES） - 绿色荧光蛋白（GFP）元件。发现这些小鼠细胞中的GFP荧光与IL - 10蛋白表达呈正相关。利用该模型，我们发现在多次T细胞受体（TCR）刺激后，小肠上皮内淋巴细胞（IEL）和结肠固有层淋巴细胞（cLPL）特异性地产生强烈的IL - 10表达。我们发现抗CD3治疗在小肠上皮内淋巴细胞（sIEL）中诱导产生1型调节性T细胞（Tr1）样细胞，并导致结肠固有层淋巴细胞（cLPL）中天然存在的调节性T细胞（nTreg）的积累。这些发现强调肠道是诱导产生IL - 10的T细胞的独特部位，其在肠道炎症的调节中起关键作用。
To identify interleukin-10 (IL-10)-producing cells in vivo, we generated a knockin mouse where an internal ribosome entry site (IRES) green fluorescence protein (GFP) element was inserted immediately before the polyadenylation site of the IL-10 gene. GFP fluorescence in cells from these mice was found to correlate positively with IL-10 protein expression. With this model, we found that after multiple T cell receptor (TCR) stimulations, strong expression of IL-10 was produced specifically by intraepithelial lymphocytes (IEL) in the small intestine and colonic lamina propria lymphocytes (cLPL). We found that anti-CD3 treatment induces T regulatory cell 1 (Tr1)-like cells in small intestinal IEL (sIEL) and led to the accumulation of naturally occurring regulatory T (nTreg) cells in colonic LPL (cLPL). These findings highlight the intestine as a unique site for induction of IL-10-producing T cells, which play a critical role in the regulation of inflammation in the gut.