Transforming growth factor-β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells.

Abstract:

:Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful pathogens. Together with T cells, the various ILC3 subsets maintain the balance between homeostasis and immune activation. Through genetic mapping, we identified a previously uncharacterized subset of NCR(-) ILC3s in mice that transiently express Ncr1, demonstrating previously undescribed heterogeneity within the ILC3 population. In addition, we showed that sustained Notch signaling was required for the maintenance of the NCR(+) phenotype and that the cytokine transforming growth factor-β (TGF-β) impaired the development of NCR(+) ILC3s. Thus, the plasticity of ILC3s is regulated by the balance between the opposing effects of Notch and TGF-β signaling, maintaining homeostasis in the face of continual challenges.

journal_name

Sci Signal

journal_title

Science signaling

authors

Viant C,Rankin LC,Girard-Madoux MJ,Seillet C,Shi W,Smyth MJ,Bartholin L,Walzer T,Huntington ND,Vivier E,Belz GT

doi

10.1126/scisignal.aaf2176

subject

Has Abstract

pub_date

2016-05-03 00:00:00

pages

ra46

issue

426

eissn

1945-0877

issn

1937-9145

pii

9/426/ra46

journal_volume

9

pub_type

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