The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation

Shadi Swaidani; Katarzyna Bulek; Zizhen Kang; Caini Liu; Yi Lu; Weiguo Yin; Mark Aronica; Xiaoxia Li

doi:10.4049/jimmunol.182.3.1631

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The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation

Journal article

Open access

Peer reviewed

The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation

Shadi Swaidani, Katarzyna Bulek, Zizhen Kang, Caini Liu, Yi Lu, Weiguo Yin, Mark Aronica and Xiaoxia Li

The Journal of immunology (1950), Vol.182(3), pp.1631-1640

02/01/2009

DOI: 10.4049/jimmunol.182.3.1631

PMCID: PMC3015148

PMID: 19155512

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https://www.ncbi.nlm.nih.gov/pmc/articles/3015148View

Open Access

Abstract

IL-25 initiates, promotes, and augments Th2 immune responses. In this study, we report that Act1, a key component in IL-17-mediated signaling, is an essential signaling molecule for IL-25 signaling. Although Act1-deficient mice showed reduced expression of KC (CXCL1) and neutrophil recruitment to the airway compared with wild-type mice in response to IL-17 stimulation, Act1 deficiency abolished IL-25-induced expression of IL-4, IL-5, IL-13, eotaxin-1 (CCL11), and pulmonary eosinophilia. Using a mouse model of allergic pulmonary inflammation, we observed diminished Th2 responses and lung inflammation in Act1-deficient mice compared with wild-type mice. Importantly, Act1 deficiency in epithelial cells reduced the phenotype of allergic pulmonary inflammation due to loss of IL-17-induced neutrophilia and IL-25-induced eosinophilia, respectively. These results demonstrate the essential role of epithelial-derived Act1 in allergic pulmonary inflammation through the distinct impact of the IL-17R-Act1 and IL-25R-Act1 axes. Such findings are crucial for the understanding of pathobiology of atopic diseases, including allergic asthma, which identifies Act1 as a potential therapeutic target.

Adaptor Proteins, Signal Transducing - deficiency

Adaptor Proteins, Signal Transducing - genetics

Adaptor Proteins, Signal Transducing - physiology

Animals

Bronchoalveolar Lavage Fluid - cytology

Bronchoalveolar Lavage Fluid - immunology

Cells, Cultured

Eosinophilia - immunology

Eosinophilia - metabolism

Eosinophilia - prevention & control

Female

HeLa Cells

Humans

Inflammation Mediators - physiology

Interleukin-17 - administration & dosage

Interleukin-17 - physiology

Interleukins - administration & dosage

Interleukins - physiology

Lung - immunology

Lung - metabolism

Lung - pathology

Mice

Mice, Inbred BALB C

Mice, Inbred C57BL

Mice, Knockout

Mice, Transgenic

Respiratory Hypersensitivity - immunology

Respiratory Hypersensitivity - metabolism

Respiratory Hypersensitivity - pathology

Respiratory Mucosa - immunology

Respiratory Mucosa - metabolism

Respiratory Mucosa - pathology

Details

Title: Subtitle: The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation
Creators: Shadi Swaidani - Cleveland Clinic
Katarzyna Bulek - *Department of Immunology and
Zizhen Kang - *Department of Immunology and
Caini Liu - *Department of Immunology and
Yi Lu - *Department of Immunology and
Weiguo Yin - *Department of Immunology and
Mark Aronica - Cleveland Clinic
Xiaoxia Li - *Department of Immunology and
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.182(3), pp.1631-1640
DOI: 10.4049/jimmunol.182.3.1631
PMID: 19155512
PMCID: PMC3015148
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 HL098935 / NHLBI NIH HHS R01 AI065470 / NIAID NIH HHS R01 AI065470-05 / NIAID NIH HHS R01AI065470 / NIAID NIH HHS
Language: English
Date published: 02/01/2009
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984201115002771

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