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// Ying Lu 1 , Xianyu Zhang 1 , Nicolas Bouladoux 2 , Saransh Neel Kaul 3 , Kangxin Jin 4 , Derek Sant’Angelo 5 , Yasmine Belkaid 2 and Damian Kovalovsky 1,6 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 Abstract 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. |
