IL-1β, IL-4 and IL-12 Control the Fate of Group 2 Innate Lymphoid Cells in Human Airway Inflammation in the Lungs

Overview

Journal Nat Immunol

Date 2016 Apr 26

PMID 27111145

Citations 235

Authors

Suzanne M Bal

Jochem H Bernink

Maho Nagasawa

Jelle Groot

Medya M Shikhagaie

Kornel Golebski

Cornelis M Van Drunen

Rene Lutter

Rene E Jonkers

Pleun Hombrink

Melanie Bruchard

Julien Villaudy

J Marius Munneke

Wytske Fokkens

Jonas S Erjefalt

Hergen Spits

Xavier Romero Ros

Affiliations

Soon will be listed here.

Abstract

Group 2 innate lymphoid cells (ILC2s) secrete type 2 cytokines, which protect against parasites but can also contribute to a variety of inflammatory airway diseases. We report here that interleukin 1β (IL-1β) directly activated human ILC2s and that IL-12 induced the conversion of these activated ILC2s into interferon-γ (IFN-γ)-producing ILC1s, which was reversed by IL-4. The plasticity of ILCs was manifested in diseased tissues of patients with severe chronic obstructive pulmonary disease (COPD) or chronic rhinosinusitis with nasal polyps (CRSwNP), which displayed IL-12 or IL-4 signatures and the accumulation of ILC1s or ILC2s, respectively. Eosinophils were a major cellular source of IL-4, which revealed cross-talk between IL-5-producing ILC2s and IL-4-producing eosinophils. We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation.

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