Interleukin-12 and-23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

被引：583

作者：

Bernink, Jochem H. ^{[1
]}

Krabbendam, Lisette ^{[1
]}

Germar, Kristine ^{[1
]}

de Jong, Esther ^{[1
]}

Gronke, Konrad ^{[5
,6
]}

Kofoed-Nielsen, Michael ^{[5
,6
]}

Munneke, J. Marius ^{[2
]}

Hazenberg, Mette D. ^{[2
]}

Villaudy, Julien ^{[3
]}

Buskens, Christianne J. ^{[4
]}

Bemelman, Willem A. ^{[4
]}

Diefenbach, Andreas ^{[5
,6
]}

Blom, Bianca ^{[1
]}

Spits, Hergen ^{[1
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands

[3] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Surg, NL-1105 AZ Amsterdam, Netherlands

[5] Johannes Gutenberg Univ Mainz, Med Ctr, Immunol Res Ctr, D-55131 Mainz, Germany

[6] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Med Microbiol & Hyg, D-55131 Mainz, Germany

来源：

IMMUNITY | 2015年 / 43卷 / 01期

基金：

欧洲研究理事会;

关键词：

T-BET; RETINOIC-ACID; T(H)17 DIFFERENTIATION; DENDRITIC CELLS; INFLAMMATION; EXPRESSION; INSIGHTS;

D O I：

10.1016/j.immuni.2015.06.019

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：146 / 160

页数：15

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