CD11b+ Myeloid Cells Are the Key Mediators of Th2 Cell Homing into the Airway in Allergic Inflammation

被引:103
作者
Medoff, Benjamin D. [1 ,2 ,3 ,4 ]
Seung, Edward [1 ,2 ]
Hong, Sandra [1 ,2 ]
Thomas, Seddon Y. [1 ,2 ]
Sandall, Barry P. [1 ,2 ,3 ,4 ]
Duffield, Jeremy S. [5 ,6 ,7 ]
Kuperman, Douglas A. [8 ]
Erle, David J. [9 ,10 ]
Luster, Andrew D. [1 ,2 ]
机构
[1] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA
[2] Harvard Univ, Sch Med, Charlestown, MA 02129 USA
[3] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Boston, MA 02114 USA
[5] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA
[6] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Boston, MA 02115 USA
[8] Northwestern Univ, Feinberg Sch Med, Div Allergy Immunol, Chicago, IL 60611 USA
[9] Univ Calif San Francisco, Lung Biol Ctr, Dept Med, Cardiovasc Res Inst, San Francisco, CA 94143 USA
[10] Univ Calif San Francisco, Program Immunol, San Francisco, CA 94143 USA
基金
美国国家卫生研究院;
关键词
ACTIVATION-REGULATED CHEMOKINE; THYMIC STROMAL LYMPHOPOIETIN; EPITHELIAL-CELLS; LUNG INFLAMMATION; DENDRITIC CELL; EXPERIMENTAL ASTHMA; EOTAXIN EXPRESSION; SIGNAL TRANSDUCER; MUCUS PRODUCTION; TYPE-2; IMMUNITY;
D O I
10.4049/jimmunol.182.1.623
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
STAT6-mediated chemokine production in the lung is required for Th2 lymphocyte and eosinophil homing into the airways in allergic pulmonary inflammation, and thus is a potential therapeutic target in asthma. However, the critical cellular source of STAT6-mediated chemokine production has not been defined. In this study, we demonstrate that STAT6 in bone marrow-derived myeloid cells was sufficient for the production of CCL17, CCL22, CCL11, and CCL24 and for Th2 lymphocyte and eosinophil recruitment into the allergic airway. In contrast, STAT6 in airway-lining cells did not mediate chemokine production or support cellular recruitment. Selective depletion of CD11b(+) myeloid cells in the lung identified these cells as the critical cellular source for the chemokines CCL17 and CCL22. These data reveal that CD11b(+) myeloid cells in the lung help orchestrate the adaptive immune response in asthma, in part, through the production of STAT6-inducible chemokines and the recruitment of Th2 lymphocytes into the airway. The Journal of Immunology, 2009, 182: 623-635.
引用
收藏
页码:623 / 635
页数:13
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