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

Steward-Tharp, Scott M; Laurence, Arian; Kanno, Yuka; Kotlyar, Alex; Villarino, Alejandro V; Sciume, Giuseppe; Kuchen, Stefan; Resch, Wolfgang; Wohlfert, Elizabeth A; Jiang, Kan; Hirahara, Kiyoshi; Vahedi, Golnaz; Sun, Hong-Wei; Feigenbaum, Lionel; Milner, Joshua D; Holland, Steven M; Casellas, Rafael; Powrie, Fiona; O'Shea, John J (2014). A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3. Blood, 123(19), pp. 2978-2987. American Society of Hematology 10.1182/blood-2013-09-523167

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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. We found 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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Kuchen, Stefan


600 Technology > 610 Medicine & health




American Society of Hematology




Stefan Kuchen

Date Deposited:

06 Mar 2015 15:11

Last Modified:

06 Mar 2015 15:11

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