Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands

被引：206

作者：

Cortez, Victor S. ^{[1
]}

Cervantes-Barragan, Luisa ^{[1
]}

Robinette, Michelle L. ^{[1
]}

Bando, Jennifer K. ^{[1
]}

Wang, Yaming ^{[1
]}

Geiger, Theresa L. ^{[2
]}

Gilfillan, Susan ^{[1
]}

Fuchs, Anja ^{[3
]}

Vivier, Eric ^{[4
]}

Sun, Joe C. ^{[2
]}

Cella, Marina ^{[1
]}

Colonna, Marco ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63108 USA

[2] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA

[3] Washington Univ, Sch Med, Dept Surg, Sect Acute & Crit Care Surg, St Louis, MO 63108 USA

[4] UM2 Aix Marseille Univ, Ctr Immunol Marseille Luminy, Marseille, France

来源：

IMMUNITY | 2016年 / 44卷 / 05期

关键词：

MEMORY T-CELLS; TGF-BETA; TRANSCRIPTIONAL REGULATION; NFIL3; EXPRESSION; INDUCTION; INFECTION; EFFECTOR; ISOFORMS; LIVER;

D O I：

10.1016/j.immuni.2016.03.007

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：

The signals guiding differentiation of innate lymphoid cells (ILCs) within tissues are not well understood. Salivary gland (SG) ILCs as well as liver and intestinal intraepithelial ILC1 have markers that denote tissue residency and transforming growth factor-beta (TGF-beta) imprinting. We deleted Tgfbr2 in cells expressing the ILC and NK marker NKp46 and found that SG ILCs were reduced in number. They lost distinct tissue markers, such as CD49a, and the effector molecules TRAIL and CD73. Expression of the transcription factor Eomes, which promotes NK cell differentiation, was elevated. Conversely, Eomes deletion in NKp46(+) cells enhanced TGF-beta-imprinting of SG ILCs. Thus, TGF-beta induces SG ILC differentiation by suppressing Eomes. TGF-beta acted through a JNK-dependent, Smad4-independent pathway. Transcriptome analysis demonstrated that SG ILCs had characteristic of both NK cells and ILC1. Finally, TGF-beta imprinting of SG ILCs was synchronized with SG development, highlighting the impact of tissue microenvironment on ILC development.

引用

页码：1127 / 1139

页数：13

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