title: A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3.
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. 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.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Scott M
authors.initials: SM
authors.lastname: Steward-Tharp
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: Alex
authors.initials: A
authors.lastname: Kotlyar
authors.forename: Alejandro V
authors.initials: AV
authors.lastname: Villarino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciume
authors.forename: Stefan
authors.initials: S
authors.lastname: Kuchen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Resch
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wohlfert
authors.forename: Kan
authors.initials: K
authors.lastname: Jiang
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.forename: Golnaz
authors.initials: G
authors.lastname: Vahedi
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Sun
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Rafael
authors.initials: R
authors.lastname: Casellas
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D044082:Citrobacter rodentium / Q000276:immunology / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D008070:Lipopolysaccharides; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D012772:Shock, Septic / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D059467:Transcriptome / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; D007073:Immunoglobulin E