Epithelial Cell-Specific Act1 Adaptor Mediates Interleukin-25-Dependent Helminth Expulsion through Expansion of Lin−c-Kit+ Innate Cell Population

Zizhen Kang; Shadi Swaidani; Weiguo Yin; Chenhui Wang; Jillian L Barlow; Muhammet Fatih Gulen; Katarzyna Bulek; Jeong-su Do; Mark Aronica; Andrew N.J McKenzie; Booki Min; Xiaoxia Li

doi:10.1016/j.immuni.2012.03.021

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Epithelial Cell-Specific Act1 Adaptor Mediates Interleukin-25-Dependent Helminth Expulsion through Expansion of Lin−c-Kit+ Innate Cell Population

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Epithelial Cell-Specific Act1 Adaptor Mediates Interleukin-25-Dependent Helminth Expulsion through Expansion of Lin−c-Kit+ Innate Cell Population

Zizhen Kang, Shadi Swaidani, Weiguo Yin, Chenhui Wang, Jillian L Barlow, Muhammet Fatih Gulen, Katarzyna Bulek, Jeong-su Do, Mark Aronica, Andrew N.J McKenzie, …

Immunity (Cambridge, Mass.), Vol.36(5), pp.821-833

05/25/2012

DOI: 10.1016/j.immuni.2012.03.021

PMCID: PMC3376903

PMID: 22608496

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Abstract

Interleukin-25 (IL-25 or IL-17E), a member of the structurally related IL-17 family, functions as an important mediator of T helper 2 cell-type (type 2) responses. We examined the cell type-specific role of IL-25-induced Act1-mediated signaling in protective immunity against helminth infection. Targeted Act1 deficiency in epithelial cells resulted in a marked delay in worm expulsion and abolished the expansion of the Lin−c-Kit+ innate cell population in the mesenteric lymph node, lung, and liver. Th2 cell-inducing cytokine (IL-25 and IL-33) expression were reduced in the intestinal epithelial cells from the infected and IL-25-injected epithelial-specific Act1-deficient mice. Adoptive transfer of Lin−c-Kit+ cells or combined injection of IL-25 and IL-33 restored the type 2 responses in these mice. Taken together, these results suggest that epithelial-specific Act1 mediates the expansion of the Lin−c-Kit+ innate cell population through the positive-feedback loop of IL-25, initiating the type 2 immunity against helminth infection. ► Epithelial cell-specific Act1 is critical for IL-25-dependent helminth expulsion ► Act1 in epithelium is required for IL-25-induced expansion of Lin−c-Kit+ cells ► Epithelial cells produce IL-25, etc., to induce the expansion of the Lin−c-Kit+ cells ► Lin−c-Kit+ cells rescued type 2 immunity in epithelial-specific Act1-deficient mice

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Title: Subtitle: Epithelial Cell-Specific Act1 Adaptor Mediates Interleukin-25-Dependent Helminth Expulsion through Expansion of Lin−c-Kit+ Innate Cell Population
Creators: Zizhen Kang - Cleveland Clinic
Shadi Swaidani - Cleveland Clinic
Weiguo Yin - Cleveland Clinic
Chenhui Wang - Cleveland Clinic
Jillian L Barlow - MRC Laboratory of Molecular Biology
Muhammet Fatih Gulen - Cleveland Clinic
Katarzyna Bulek - Cleveland Clinic
Jeong-su Do - Cleveland Clinic
Mark Aronica - Cleveland Clinic
Andrew N.J McKenzie - MRC Laboratory of Molecular Biology
Booki Min - Cleveland Clinic
Xiaoxia Li - Cleveland Clinic
Resource Type: Journal article
Publication Details: Immunity (Cambridge, Mass.), Vol.36(5), pp.821-833
DOI: 10.1016/j.immuni.2012.03.021
PMID: 22608496
PMCID: PMC3376903
NLM abbreviation: Immunity
ISSN: 1074-7613
eISSN: 1097-4180
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: RO1HL098935-01A1, 09-0035, AI080908
Language: English
Date published: 05/25/2012
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984201248702771

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