Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes.
Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt(+) innate lymphocytes.
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DOI：
10.1016/j.immuni.2010.10.017
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发表时间：
2010-11-24
期刊：
影响因子：
32.4
通讯作者：
Diefenbach A
中科院分区：
文献类型：
--
作者：
Vonarbourg C;Mortha A;Bui VL;Hernandez PP;Kiss EA;Hoyler T;Flach M;Bengsch B;Thimme R;Hölscher C;Hönig M;Pannicke U;Schwarz K;Ware CF;Finke D;Diefenbach A
最近发现的先天淋巴细胞群是否共同表达自然杀伤细胞受体（NKRs）和核受体rr γt是NK或淋巴组织诱导剂（LTi）细胞谱系的一部分尚不清楚。通过对遗传标记的lti样细胞的过继转移，我们证明了NKR - RORγt+先天淋巴细胞是NKR+RORγt+细胞的直接祖细胞，而不是NK细胞。遗传谱系追踪显示，lti样细胞分化的特征是NKRs的稳定上调和rorγ - t表达的逐渐丧失。白细胞介素-7 （IL-7）和肠道微生物群稳定了NKR-LTi细胞中RORγt的表达，而IL-12和IL-15则加速了RORγt的损失。RORγt+ NKR-LTi细胞产生IL-22，而RORγt - NKR-LTi细胞释放IFN-γ，是结肠炎的有效诱导因子。因此，NKR-LTi细胞中的rorγ - t梯度可作为其功能程序的可调变阻器。我们的数据还定义了rorγ - t - NKR-LTi细胞在炎症性肠病发病或维持中的作用。
Whether the recently identified innate lymphocyte population co-expressing natural killer cell receptors (NKRs) and the nuclear receptor RORγt is part of the NK or lymphoid tissue inducer (LTi) cell lineage remains unclear. Using adoptive transfer of genetically tagged LTi-like cells, we demonstrate that NKR−RORγt+ innate lymphocytes but not NK cells were direct progenitors to NKR+RORγt+ cells in vivo. Genetic lineage tracing revealed that the differentiation of LTi-like cells was characterized by the stable upregulation of NKRs and a progressive loss of RORγt expression. Whereas interleukin-7 (IL-7) and intestinal microbiota stabilized RORγt expression within such NKR-LTi cells, IL-12 and IL-15 accelerated RORγt loss. RORγt+ NKR-LTi cells produced IL-22, whereas RORγt− NKR-LTi cells released IFN-γ and were potent inducers of colitis. Thus, the RORγt gradient in NKR-LTi cells serves as a tunable rheostat for their functional program. Our data also define a previously unappreciated role of RORγt− NKR-LTi cells for the onset or maintenance of inflammatory bowel diseases.
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影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
DOI：
10.1084/jem.20021294
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luther SA;Ansel KM;Cyster JG
通讯作者：
Cyster JG
影响因子：
32.4
作者：
Oppmann, B;Lesley, R;Kastelein, RA
通讯作者：
Kastelein, RA
影响因子：
15.9
作者：
Lai, SY;Molden, J;Goldsmith, MA
通讯作者：
Goldsmith, MA
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.