The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway Academic Article uri icon

abstract

  • NKp46+ innate lymphoid cells (ILCs) serve important roles in regulating the intestinal microbiota and defense against pathogens. Whether NKp46+ ILCs arise directly from lymphoid tissue-inducer (LTi) cells or represent a separate lineage remains controversial. We report here that the transcription factor T-bet (encoded by Tbx21) was essential for the development of NKp46+ ILCs but not of LTi cells or nuocytes. Deficiency in interleukin 22 (IL-22)-producing NKp46+ ILCs resulted in greater susceptibility of Tbx21-/- mice to intestinal infection. Haploinsufficient T-bet expression resulted in lower expression of the signaling molecule Notch, and Notch signaling was necessary for the transition of LTi cells into NKp46+ ILCs. Furthermore, NKp46+ ILCs differentiated solely from the CD4- LTi population, not the CD4+ LTi population. Our results pinpoint the regulation of Notch signaling by T-bet as a distinct molecular pathway that guides the development of NKp46+ ILCs.

authors

  • Rankin, Lucille C
  • Groom, Joanna R
  • Chopin, Michaël
  • Herold, Marco J
  • Walker, Jennifer A
  • Mielke, Lisa A
  • McKenzie, Andrew NJ
  • Carotta, Sebastian
  • Nutt, Stephen L
  • Belz, Gabrielle T

publication date

  • 2013