IL-33 is more potent than IL-25 in provoking IL-13–producing nuocytes (type 2 innate lymphoid cells) and airway contraction

Barlow, Jillian L.; Peel, Samantha; Fox, Jane; Panova, Veera; Hardman, Clare S.; Camelo, Ana Paula; Bucks, Christine M.; Wu, Xiaoying; Kane, Colleen; Neill, Daniel R.; Flynn, Robin J.; Sayers, Ian; Hall, Ian P.; McKenzie, Andrew N. J.

doi:10.1016/j.jaci.2013.05.012

Cited by 346 publications

(335 citation statements)

References 46 publications

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“…In agreement with these findings, BAL fluids from HDM-challenged mice demonstrated increased levels of IL-33, as well as the type 2 cytokines IL-5 and IL-13 ( Figure 4B), which were associated with corresponding increases in lung tissue mRNA levels (Supplemental Figure 2B), and each of these responses was dramatically suppressed in HDM-treated Duox1 -/-mice. Serum levels of HDM-specific IgG1 and IgE indicated were highly similar between HDM-challenged wild-type and Duox1 -/-mice (Supplemental Figure 2C), suggesting that DUOX1-dependent type 2 responses are largely independent of adaptive immune responses and are most likely related to expansion and activation of ILC2s, which could serve as the primary source of IL-5, IL-3, and the EGFR ligand AREG in response to epithelial-derived cytokines, such as IL-33, within the lung (31)(32)(33). To address this, we generated single-cell suspensions of lung tissues from both control and HDM-challenged mice for in vitro restimulation with IL-33, which revealed dramatically enhanced production of IL-5, IL-13, and Areg by lung cell suspensions from HDM-challenged wild-type mice but not from Duox1 -/-mice ( Figure 4C).…”

Section: Resultsmentioning

confidence: 90%

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Habibovic¹,

Hristova²,

Heppner³

et al. 2016

JCI Insight

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Section: Resultsmentioning

confidence: 90%

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Habibovic¹,

Hristova²,

Heppner³

et al. 2016

JCI Insight

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“…For example, the potential tissue-specific factors that regulate ILC2s are complex and remain poorly understood. The current body of evidence suggests that IL-33 may be the dominant cytokine for the activation of lung and airway ILC2s (Mjosberg et al 2012;Monticelli et al 2012;Barlow et al 2013), whereas IL-25 is critical for their role in gut inflammation . However, IL-25 may also play a role in the regulation of pulmonary fibrosis (Hams et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Group 2 Innate Lymphoid Cells in Health and Disease

Kim

Artis

2015

Cold Spring Harb Perspect Biol

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Group 2 innate lymphoid cells (ILC2s) play critical roles in anti-helminth immunity, airway epithelial repair, and metabolic homeostasis. Recently, these cells have also emerged as key players in the development of allergic inflammation at multiple barrier surfaces. ILC2s arise from common lymphoid progenitors in the bone marrow, are dependent on the transcription factors RORa, GATA3, and TCF-1, and produce the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, and/or IL-13. The epithelial cell -derived cytokines IL-25, IL-33, and TSLP regulate the activation and effector functions of ILC2s, and recent studies suggest that their responsiveness to these cytokines and other factors may depend on their tissue environment. In this review, we focus on recent advances in our understanding of the various factors that regulate ILC2 function in the context of immunity, inflammation, and tissue repair across multiple organ systems.

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“…These results suggest the hypothesis that ATG16L1 function plays a role in goblet cell secretion in IL33-induced goblet cell metaplasia as indicated by an increase in airway goblet cells that supplant the normal ciliated and nongoblet secretory cell populations. 34 As IL33 is well known to induce goblet cell metaplasia, as a pathological response to IL13, 34 this further suggests that IL13 is the factor that acts directly on lung airway epithelial cells.…”

Section: Il33-induced Airway Goblet Cell Hypertrophy In Atg16l1-deficmentioning

confidence: 99%

IL13 activates autophagy to regulate secretion in airway epithelial cells

et al. 2016

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Cytokine modulation of autophagy is increasingly recognized in disease pathogenesis, and current concepts suggest that type 1 cytokines activate autophagy, whereas type 2 cytokines are inhibitory. However, this paradigm derives primarily from studies of immune cells and is poorly characterized in tissue cells, including sentinel epithelial cells that regulate the immune response. In particular, the type 2 cytokine IL13 (interleukin 13) drives the formation of airway goblet cells that secrete excess mucus as a characteristic feature of airway disease, but whether this process is influenced by autophagy was undefined. Here we use a mouse model of airway disease in which IL33 (interleukin 33) stimulation leads to IL13-dependent formation of airway goblet cells as tracked by levels of mucin MUC5AC (mucin 5AC, oligomeric mucus/gel forming), and we show that these cells manifest a block in mucus secretion in autophagy gene Atg16l1-deficient mice compared to wild-type control mice. Similarly, primary-culture human tracheal epithelial cells treated with IL13 to stimulate mucus formation also exhibit a block in MUC5AC secretion in cells depleted of autophagy gene ATG5 (autophagy-related 5) or ATG14 (autophagyrelated 14) compared to nondepleted control cells. Our findings indicate that autophagy is essential for airway mucus secretion in a type 2, IL13-dependent immune disease process and thereby provide a novel therapeutic strategy for attenuating airway obstruction in hypersecretory inflammatory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis lung disease. Taken together, these observations suggest that the regulation of autophagy by Th2 cytokines is cell-context dependent.

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IL-33 is more potent than IL-25 in provoking IL-13–producing nuocytes (type 2 innate lymphoid cells) and airway contraction

Cited by 346 publications

References 46 publications

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Group 2 Innate Lymphoid Cells in Health and Disease

IL13 activates autophagy to regulate secretion in airway epithelial cells

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