title: Dynamic control of Th2 cell responses by STAT3 during allergic lung inflammation in mice.
abstract: Signal transducer and activator of transcription (STAT) family molecules play essential roles during the differentiation of helper T cells from naïve precursors. Although the role of STAT3 in driving Th17 cell polarization has been well established, its role on Th2 responses to allergens remains incompletely understood. By employing T cell-specific STAT3 deficient mice, we demonstrate that STAT3 in T cells plays diverse role on Th2 cells depending on their locations in an animal model of allergic asthma. In the bronchial lymph nodes, STAT3-deficient T cells produced significantly reduced levels of Th2 cytokines. The frequencies of Th2 cells among CD4(+) T cells in the lung were comparable between STAT3-sufficient and STAT3-deficient T cells. By contrast, STAT3-deficient T cells in the airway exhibited significantly enhanced production of Th2 cell cytokines compared to STAT3-sufficient T cells. Interestingly, a major population of IL-4/5 producers among STAT3-deficient T cells in the airway co-produced IFNγ. The frequency of Th17 cells was significantly diminished whereas that of Th1 cells was increased in all the lung-associated tissues. Our results demonstrate the dynamic and opposing roles of STAT3 during the development of Th2 cells from bronchial lymph nodes to the airway and propose the need of careful consideration on STAT3-targeting approaches for the treatment of lung diseases.
authors: Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Hoyong
authors: H
authors: Lim
authors: Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Minkyoung
authors: M
authors: Cho
authors: Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Garam
authors: G
authors: Choi
authors: Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Hyeongjin
authors: H
authors: Na
authors: Laboratory of Immune Regulation, Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: yeonseok@snu.ac.kr.
authors: Yeonseok
authors: Y
authors: Chung
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001230:Aspergillus / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D008168:Lung / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010447:Peptide Hydrolases / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D000485:Allergens; D000946:Antigens, Fungal; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D010047:Ovalbumin; D010447:Peptide Hydrolases
keywords: Allergic asthma; STAT3; Th1 cell; Th17 cell; Th2 cell