TY - JOUR
T1 - IL-15 sustains IL-7R-independent ILC2 and ILC3 development
AU - Robinette, Michelle L.
AU - Bando, Jennifer K.
AU - Song, Wilbur
AU - Ulland, Tyler K.
AU - Gilfillan, Susan
AU - Colonna, Marco
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/3/31
Y1 - 2017/3/31
N2 - The signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra-/- mice. Il7ra-/- ILC2 primarily express an ST2- phenotype, but are not inflammatory ILC2. CCR6+ ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra-/- siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra-/- ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling.
AB - The signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra-/- mice. Il7ra-/- ILC2 primarily express an ST2- phenotype, but are not inflammatory ILC2. CCR6+ ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra-/- siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra-/- ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling.
UR - http://www.scopus.com/inward/record.url?scp=85016587498&partnerID=8YFLogxK
U2 - 10.1038/ncomms14601
DO - 10.1038/ncomms14601
M3 - Article
C2 - 28361874
AN - SCOPUS:85016587498
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
M1 - 14601
ER -