The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway.
Nat Immunol
; 14(4): 389-95, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23455676
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Antígenos Ly
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Subgrupos Linfocitarios
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Proteínas de Dominio T Box
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Receptores Notch
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Receptor 1 Gatillante de la Citotoxidad Natural
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Inmunidad Innata
Límite:
Animals
Idioma:
En
Año:
2013
Tipo del documento:
Article