STAT6 Expression in Multiple Cell Types Mediates the Cooperative Development of Allergic Airway Disease

被引:36
作者
Chapoval, Svetlana P. [1 ,2 ,3 ]
Dasgupta, Preeta [1 ,2 ]
Smith, Elizabeth P. [1 ]
DeTolla, Louis J. [4 ]
Lipsky, Michael M. [4 ]
Kelly-Welch, Ann E. [1 ]
Keegan, Achsah D. [1 ,2 ,3 ]
机构
[1] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Program Oncol, Baltimore, MD 21201 USA
[4] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA
基金
美国国家卫生研究院;
关键词
REGULATORY T-CELLS; IN-VIVO; DENDRITIC CELLS; TRANSGENIC MICE; BAROMETRIC PLETHYSMOGRAPHY; ACTIVATED MACROPHAGES; SIGNAL TRANSDUCER; IL-4; INFLAMMATION; ASTHMA;
D O I
10.4049/jimmunol.1002567
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Th2 cells induce asthma through the secretion of cytokines. Two such cytokines, IL-4 and IL-13, are critical mediators of many features of this disease. They both share a common receptor subunit, IL-4R alpha, and signal through the STAT6 pathway. STAT6(-/-) mice have impaired Th2 differentiation and reduced airway response to allergen. Transferred Th2 cells were not able to elicit eosinophilia in response to OVA in STAT6(-/-) mice. To clarify the role of STAT6 in allergic airway inflammation, we generated mouse bone marrow (BM) chimeras. We observed little to no eosinophilia in OVA-treated STAT6(-/-) mice even when STAT6(+/+) BM or Th2 cells were provided. However, when Th2 cells were transferred to STAT6xRag2(-/-) mice, we observed an eosinophilic response to OVA. Nevertheless, the expression of STAT6 on either BM-derived cells or lung resident cells enhanced the severity of OVA-induced eosinophilia. Moreover, when both the BM donor and recipient lacked lymphocytes, transferred Th2 cells were sufficient to induce the level of eosinophilia comparable with that of wild-type (WT) mice. The expression of STAT6 in BM-derived cells was more critical for the enhanced eosinophilic response. Furthermore, we found a significantly higher number of CD4(+)CD25(+)Foxp3(+) T cells (regulatory T cells [Tregs]) in PBS- and OVA-treated STAT6(-/-) mouse lungs compared with that in WT animals suggesting that STAT6 limits both naturally occurring and Ag-induced Tregs. Tregs obtained from either WT or STAT6(-/-) mice were equally efficient in suppressing CD4(+) T cell proliferation in vitro. Taken together, our studies demonstrate multiple STAT6-dependent and -independent features of allergic inflammation, which may impact treatments targeting STAT6. The Journal of Immunology, 2011, 186: 2571-2583.
引用
收藏
页码:2571 / 2583
页数:13
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