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Unique and redundant functions of NKp46+ ILC3s in models of intestinal inflammation

Authors :
Song, Christina
Lee, Jacob S.
Gilfillan, Susan
Robinette, Michelle L.
Newberry, Rodney D.
Stappenbeck, Thaddeus S.
Mack, Matthias
Cella, Marina
Colonna, Marco
Source :
The Journal of Experimental Medicine; October 2015, Vol. 212 Issue: 11 p1869-1882, 14p
Publication Year :
2015

Abstract

Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissue-inducer (LTi)-like and NKp46+ subsets. Both depend on RORγt and aryl hydrocarbon receptor, but NKp46+ILC3s also require Notch and T-bet for their development and are transcriptionally distinct. The extent to which these subsets have unique functions, especially in the context of T cell– and B cell–sufficient mice, remains largely unclear. To investigate the specific function of NKp46+ILC3s among other ILC3 subsets and T cells, we generated mice selectively lacking NKp46+ILC3s or all ILC3s and crossed them to T cell–deficient mice, thus maintaining B cells in all mice. In mice lacking T cells, NKp46+ILC3s were sufficient to promote inflammatory monocyte accumulation in the anti-CD40 innate colitis model through marked production of GM-CSF. In T cell–competent mice, lack of NKp46+ILCs had no impact on control of intestinal C. rodentium infection, whereas lack of all ILC3s partially impaired bacterial control. Thus, NKp46+ILC3s have a unique capacity to promote inflammation through GM-CSF–induced accumulation of inflammatory monocytes, but are superseded by LTi-like ILC3s and T cells in controlling intestinal bacterial infection.

Details

Language :
English
ISSN :
00221007 and 15409538
Volume :
212
Issue :
11
Database :
Supplemental Index
Journal :
The Journal of Experimental Medicine
Publication Type :
Periodical
Accession number :
ejs37031535
Full Text :
https://doi.org/10.1084/jem.20151403