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

Immunity 2016 05 3;44(5):1127-39. Epub 2016 May 3.

Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63108, USA. Electronic address:

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-β (TGF-β) 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-β-imprinting of SG ILCs. Thus, TGF-β induces SG ILC differentiation by suppressing Eomes. TGF-β acted through a JNK-dependent, Smad4-independent pathway. Transcriptome analysis demonstrated that SG ILCs had characteristic of both NK cells and ILC1. Finally, TGF-β imprinting of SG ILCs was synchronized with SG development, highlighting the impact of tissue microenvironment on ILC development.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.immuni.2016.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114145PMC
May 2016
29 Reads

Publication Analysis

Top Keywords

tgf-β imprinting
8
innate lymphoid
8
lymphoid cells
8
growth factor-β
8
differentiation innate
8
transforming growth
8
ilcs
6
cells
5
lost distinct
4
analysis demonstrated
4
tissue markers
4
distinct tissue
4
cd49a effector
4
pathway transcriptome
4
trail cd73
4
molecules trail
4
effector molecules
4
number lost
4
transcriptome analysis
4
markers cd49a
4

Altmetric Statistics

Similar Publications