 |
Journal articles
Gata3 drives development of RORγt+ group 3 innate lymphoid cells.
Abstract : Group 3 innate lymphoid cells (ILC3) include IL-22-producing NKp46(+) cells and IL-17A/IL-22-producing CD4(+) lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal RORγt(+) ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut RORγt(+) ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets.
Cited literature [54 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01063219
Contributor : James Di Santo <>
Submitted on : Thursday, September 11, 2014 - 4:02:40 PM
Last modification on : Monday, March 1, 2021 - 2:14:02 PM
Long-term archiving on: : Friday, December 12, 2014 - 10:46:06 AM
Contributor : James Di Santo <>
Submitted on : Thursday, September 11, 2014 - 4:02:40 PM
Last modification on : Monday, March 1, 2021 - 2:14:02 PM
Long-term archiving on: : Friday, December 12, 2014 - 10:46:06 AM
File
J_Exp_Med-2014-Serafini-jem.20...
Publisher files allowed on an open archive