Journal Article

Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation

Kojo, Satoshi, Shiroguchi, Katsuyuki, Ebihara, Takashi, Lacaud, Georges, Moro, Kazuyo, Yamashita, Motoi, Taniuchi, Ichiro, Miyamoto, Chizuko

2019

Overview

Group 2 innate lymphoid cells (ILC2s) have tissue-resident competence and contribute to the pathogenesis of allergic diseases. However, the mechanisms regulating prolonged ILC2-mediated T H 2 cytokine production under chronic inflammatory conditions are unclear. Here we show that, at homeostasis, Runx deficiency induces excessive ILC2 activation due to overly active GATA-3 functions. By contrast, during allergic inflammation, the absence of Runx impairs the ability of ILC2s to proliferate and produce effector T H 2 cytokines and chemokines. Instead, functional deletion of Runx induces the expression of exhaustion markers, such as IL-10 and TIGIT, on ILC2s. Finally, these ‘exhausted-like’ ILC2s are unable to induce type 2 immune responses to repeated allergen exposures. Thus, Runx confers competence for sustained ILC2 activity at the mucosa, and contributes to allergic pathogenesis. Group 2 innate lymphoid cells (ILC2) are important mediators for allergy, but how ILC2 are regulated under chronic inflammation is still unclear. Here the authors show that Runx transcription factors, which normally suppresses ILC2 activation at steady state, help promote ILC2 activation and type 2 cytokine production in lung allergy mouse models.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/21 / 13/31 / 38/15 / 38/91 / 49/22 / 49/31 / 49/88 / 631/250/2502 / 631/250/2504/2506 / 631/250/256/2515 / 631/250/347 / 64/60 / Allergens / Allergic diseases / Allergies / Animals / Asthma - chemically induced / Asthma - genetics / Asthma - immunology / Asthma - pathology / Bronchoalveolar Lavage Fluid - chemistry / Bronchoalveolar Lavage Fluid - immunology / Cell Proliferation / Chemokines / Clonal deletion / Core Binding Factor Alpha 2 Subunit - deficiency / Core Binding Factor Alpha 2 Subunit - genetics / Core Binding Factor Alpha 2 Subunit - immunology / Core Binding Factor beta Subunit - deficiency / Core Binding Factor beta Subunit - genetics / Core Binding Factor beta Subunit - immunology / Cytokines / Disease Models, Animal / Exhaustion / GATA-3 protein / GATA3 Transcription Factor - genetics / GATA3 Transcription Factor - immunology / Gene Expression Regulation - immunology / Homeostasis / Humanities and Social Sciences / Hypersensitivity / Immune response / Immunity, Innate / Inflammation / Interleukin 10 / Interleukin-10 - genetics / Interleukin-10 - immunology / Intestine, Small - drug effects / Intestine, Small - immunology / Intestine, Small - pathology / Liver - drug effects / Liver - immunology / Liver - pathology / Lung - drug effects / Lung - immunology / Lung - pathology / Lymphocyte Activation / Lymphocytes - classification / Lymphocytes - drug effects / Lymphocytes - immunology / Lymphocytes - pathology / Lymphocytes T / Lymphoid cells / Mice / Mice, Inbred C57BL / Mice, Transgenic / Mucosa / multidisciplinary / Papain - administration & dosage / Pathogenesis / Receptors, Immunologic - genetics / Receptors, Immunologic - immunology / Respiratory tract / Respiratory tract diseases / Science / Science (multidisciplinary) / Signal Transduction / Spleen - drug effects / Spleen - immunology / Spleen - pathology