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  1. Mairi H McLean, Education editor

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Basic science

NKp46+ group 3 innate lymphoid cells in intestinal inflammation

▸ Song C, Lee JS, Gilfillan S, et al. Unique and redundant functions of NKp46+ ILC3s in models of intestinal inflammation. J Exp Med 2015;212:1869–82.

Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that respond to changes in the tissue cytokine microenvironment by secreting effector cytokines. ILCs are divided into three major groups (ILC1–ILC3) according to the cytokines they secrete and transcription factors needed for their development. ILC3s, the focus of this article, are important for host defence against intestinal infections. In mice, ILC3s include two major subsets, LTi-like and NKp46. It is unknown whether the subsets are redundant or have specialised functions. Song and colleagues address this uncertainty by using conditional knockout mice that lack all ILC3 subsets or only NKp46+ILC3s. These strains were crossed to a strain lacking αβ and γδ T cells to assess ILC3 functions in B-cell-sufficient mice in the presence or absence of T cells. These mouse lines were examined in two models of intestinal inflammation—the anti-CD40 model of colitis and a Citrobacter rodentium infection model. In the colitis model, ILC3s elicited robust inflammation and accumulation of pathogenic Ly6C+ inflammatory monocytes that were dependent on excessive production of GM-CSF and interleukin-22 (IL-22). NKp46+ILC3s were sufficient to induce inflammation in this model, demonstrating a non-redundant inflammatory function. In the infection model, ILC3s were essential in T-cell-deficient mice but partially redundant in T-cell-competent mice. In contrast, the NKp46+ILC3 subset was always redundant, both in T-cell-competent and T-cell-deficient mice. In summary, NKp46+ILC3s have a unique role in GM-CSF-mediated recruitment and activation of inflammatory monocytes during innate intestinal inflammation, but are redundant for clearance of C. rodentium, whether T cells are present or not. For future studies, it will be important to identify the conditions under which ILC3s promote inflammation through GM-CSF and IL-22 secretion rather …

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