Interleukin-12 and-23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria
Interleukin-12 and-23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria
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DOI：
10.1016/j.immuni.2015.06.019
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发表时间：
2015-07-21
期刊：
影响因子：
32.4
通讯作者：
Spits, Hergen
中科院分区：
文献类型：
--
作者：
Bernink, Jochem H.;Krabbendam, Lisette;Spits, Hergen
人组1 ILC由至少三种表型不同的亚群组成，包括NK细胞、CD 127（+）ILC 1和上皮内CD 103（+）ILC 1。在克罗恩病患者的炎症肠组织中，CD 127（+）ILC 1的数量以ILC 3为代价增加。在此我们发现ILC 3向CD 127（+）ILC 1的分化在体外和体内都是可逆的。CD 127（+）ILC 1在白细胞介素-2（IL-2）、IL-23和IL-1 β存在下分化为ILC 3，依赖于转录因子ROR γ t，并且该过程在视黄酸存在下增强。此外，我们在克罗恩病患者的切除标本中观察到较高比例的CD 14（+）树突状细胞（DC），其在体外促进ILC 3向CD 127（+）ILC 1的极化。相反，CD 14（-）DC促进从CD 127（+）ILC 1向ILC 3的分化。这些观察结果表明，环境因素决定了肠道中CD 127（+）ILC 1和ILC 3的组成、功能和表型。
Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohn's disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo. CD127(+) ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1 beta dependent on the transcription factor ROR gamma t, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohn's disease patients a higher proportion of CD14(+) dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127(+) ILC1. In contrast, CD14(-) DCs promoted differentiation from CD127(+) ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127(+) ILC1 and ILC3 in the gut.