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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)821-833
Number of pages13
JournalImmunity
Volume36
Issue number5
DOIs
StatePublished - May 25 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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