TY - JOUR
T1 - Unique and redundant functions of NKp46+ ILC3s in models of intestinal inflammation
AU - Song, Christina
AU - Lee, Jacob S.
AU - Gilfillan, Susan
AU - Robinette, Michelle L.
AU - Newberry, Rodney D.
AU - Stappenbeck, Thaddeus S.
AU - Mack, Matthias
AU - Cella, Marina
AU - Colonna, Marco
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (1U01AI095542, R01DE021255, and R21CA16719) to M. Colonna and 1RO1CA176695 to M. Cella.
Publisher Copyright:
© 2015 Song et al.
PY - 2015/10/19
Y1 - 2015/10/19
N2 - Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissueinducer (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have a unique capacity to promote inflammation through GM-CSF-induced accumulation of inflammatory monocytes, but are superseded by LTi-like ILC3s and T cells in controlling intestinal bacterial infection.
AB - Group 3 ILCs (ILC3s) are innate sources of IL-22 and IL-17 and include lymphoid tissueinducer (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.
UR - http://www.scopus.com/inward/record.url?scp=84952869199&partnerID=8YFLogxK
U2 - 10.1084/jem.20151403
DO - 10.1084/jem.20151403
M3 - Article
C2 - 26458769
AN - SCOPUS:84952869199
SN - 0022-1007
VL - 212
SP - 1869
EP - 1882
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 11
ER -