IL-23 and IL-2 activation of STAT5 is required for optimal IL-22 production in ILC3s during colitis

David Bauché, Barbara Joyce-Shaikh, Julie Fong, Alejandro V. Villarino, Karin S. Ku, Renu Jain, Yu Chi Lee, Lakshmanan Annamalai, Jennifer H. Yearley, Daniel J. Cua

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Signal transducer and activator of transcription (STAT) proteins have critical roles in the development and function of immune cells. STAT signaling is often dysregulated in patients with inflammatory bowel disease (IBD), suggesting the importance of STAT regulation during the disease process. Moreover, genetic alterations in STAT3 and STAT5 (e.g., deletions, mutations, and single-nucleotide polymorphisms) are associated with an increased risk for IBD. In this study, we elucidated the precise roles of STAT5 signaling in group 3 innate lymphoid cells (ILC3s), a key subset of immune cells involved in the maintenance of gut barrier integrity. We show that mice lacking either STAT5a or STAT5b are more susceptible to Citrobacter rodentium-mediated colitis and that interleukin-2 (IL-2)- and IL-23-induced STAT5 drives IL-22 production in both mouse and human colonic lamina propria ILC3s. Mechanistically, IL-23 induces a STAT3-STAT5 complex that binds IL-22 promoter DNA elements in ILC3s. Our data suggest that STAT5a/b signaling in ILC3s maintains gut epithelial integrity during pathogen-induced intestinal disease.

Original languageEnglish (US)
Article numbereaav1080
JournalScience immunology
Issue number46
StatePublished - Apr 2020
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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