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

نویسندگان

  • Ying Lu
  • Xianyu Zhang
  • Nicolas Bouladoux
  • Saransh Neel Kaul
  • Kangxin Jin
  • Derek Sant’Angelo
  • Yasmine Belkaid
  • Damian Kovalovsky
چکیده

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.

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عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2017