IL-15 sustains IL-7R-independent ILC2 and ILC3 development.

Robinette, Michelle L; Bando, Jennifer K; Song, Wilbur; Ulland, Tyler K; Gilfillan, Susan; Colonna, Marco · Nat Commun · 2017

basic_science · Level V

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Abstract

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<sup>-/-</sup> mice. Il7ra<sup>-/-</sup> ILC2 primarily express an ST2<sup>-</sup> phenotype, but are not inflammatory ILC2. CCR6<sup>+</sup> ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra<sup>-/-</sup> 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<sup>-/-</sup> 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.

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