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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.

Original publication

DOI

10.1182/blood-2013-09-523167

Type

Journal article

Journal

Blood

Publication Date

08/05/2014

Volume

123

Pages

2978 - 2987

Keywords

Animals, Bone Marrow Transplantation, Cells, Cultured, Citrobacter rodentium, Cytokines, Disease Models, Animal, Enterobacteriaceae Infections, Flow Cytometry, Host-Pathogen Interactions, Humans, Immunoglobulin E, Job Syndrome, Lipopolysaccharides, Mice, Mice, Transgenic, Mutation, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor, Shock, Septic, Survival Analysis, Transcriptome