A mouse model of HIES reveals pro- And anti-inflammatory functions of STAT3

Scott M. Steward-Tharp, Arian Laurence, Yuka Kanno, Alex Kotlyar, Alejandro V. Villarino, Giuseppe Sciume, Stefan Kuchen, Wolfgang Resch, Elizabeth A. Wohlfert, Kan Jiang, Kiyoshi Hirahara, Golnaz Vahedi, Hong Wei Sun, Lionel Feigenbaum, Joshua D. Milner, Steven M. Holland, Rafael Casellas, Fiona Powrie, John J. O'Shea

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Mutations of STAT3 underlie the autosomal dominant form of hyperimmunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in nonhematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and nonhematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. Wefound that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild-type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.

Original languageEnglish (US)
Pages (from-to)2978-2987
Number of pages10
JournalBlood
Volume123
Issue number19
DOIs
StatePublished - May 8 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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