Priority Research Papers: Immunology:

Zbtb1 controls NKp46+ ROR-gamma-T+ innate lymphoid cell (ILC3) development

Ying Lu, Xianyu Zhang, Nicolas Bouladoux, Saransh Neel Kaul, Kangxin Jin, Derek Sant’Angelo, Yasmine Belkaid and Damian Kovalovsky _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:55877-55888. https://doi.org/10.18632/oncotarget.19645

Metrics: PDF 2464 views  |   HTML 3341 views  |   ?  


Ying Lu1, Xianyu Zhang1, Nicolas Bouladoux2, Saransh Neel Kaul3, Kangxin Jin4, Derek Sant’Angelo5, Yasmine Belkaid2 and Damian Kovalovsky1,6

1 Experimental Immunology Branch, NCI, NIH, Bethesda, MD, USA

2 Mucosal Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD, USA

3 University of Maryland, College Park, MD, USA

4 Zhongshan Ophthalmic Center, State Key Laboratory for Ophthalmic Researches, Sun Yat-Sen University, Guangzhou, Guangdong, China

5 Cancer Metabolism and Growth Program, Rutgers, Child Health Institute of New Jersey, New Brunswick, NJ, USA

6 Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD, USA

Correspondence to:

Damian Kovalovsky, email:

Keywords: innate lymphoid cells, ILC, ILC3, Zbtb1, IFN-γ, Immunology and Microbiology Section, Immune response, Immunity

Received: May 16, 2017 Accepted: July 14, 2017 Published: July 27, 2017


Innate lymphoid cells (ILCs) play a central role conferring protection at the mucosal frontier. In this study, we have identified a requirement of the transcription factor Zbtb1 for the development of RORγt+ ILCs (ILC3s). Zbtb1-deficient mice lacked NKp46+ ILC3 cells in the lamina propria of the small and large intestine. This requirement of Zbtb1 was cell intrinsic, as NKp46+ ILC3s were not generated from Zbtb1-deficient progenitors in bone marrow chimeras and Zbtb1-deficient RORγt+ CCR6-NKp46- ILC3s didn’t generate NKp46+ ILC3s in co-cultures with OP9-DL1 stroma. In correlation with this impairment, Zbtb1-deficient ILC3 cells failed to upregulate T-bet expression, and to acquire IFN-γ production characteristic of NKp46+ cells. Finally, absence of NKp46+ILC3 cells combined with the absence of T-cells in Zbtb1-deficient mice, led to a transient susceptibility to C. rodentium infections. Altogether, these results establish that Zbtb1 is essential for the development of NKp46+ ILC3 cells.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 19645