Lyn Kinase Controls Basophil GATA-3 Transcription Factor Expression and Induction of Th2 Cell Differentiation

被引：85

作者：

Charles, Nicolas ^{[1
]}

Watford, Wendy T. ^{[2
]}

Ramos, Haydee L. ^{[2
]}

Hellman, Lars ^{[3
]}

Oettgen, Hans C. ^{[4
]}

Gomez, Gregorio ^{[5
,6
]}

Ryan, John J. ^{[5
,6
]}

O'Shea, John J. ^{[2
]}

Rivera, Juan ^{[1
]}

机构：

[1] NIAMS, NIH, Lab Immune Cell Signaling, Bethesda, MD 20892 USA

[2] NIAMS, NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA

[3] Uppsala Univ, Dept Cell & Mol Biol, SE-75124 Uppsala, Sweden

[4] Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat,Div Immunol, Boston, MA 02115 USA

[5] Virginia Commonwealth Univ, Div Rheumatol Allergy & Immunol, Dept Internal Med, Richmond, VA 23284 USA

[6] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA

来源：

IMMUNITY | 2009年 / 30卷 / 04期

基金：

美国国家卫生研究院;

关键词：

FC-EPSILON-RI; DEFICIENT MAST-CELLS; CYTOKINE PRODUCTION; NONRELEASER BASOPHILS; NEGATIVE REGULATION; AUTOIMMUNE-DISEASE; ALLERGIC RESPONSES; HISTAMINE-RELEASE; INTERFERON-GAMMA; GENETIC-EVIDENCE;

D O I：

10.1016/j.immuni.2009.02.008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

T helper 1 (Th1)-Th2 cell balance is key to host defense and its dysregulation has pathophysiological consequences. Basophils are important in Th2 cell differentiation. However, the factors controlling the onset and extent of basophil-mediated Th2 cell differentiation are unknown. Here, we demonstrate that Lyn kinase dampened basophil expression of the transcription factor GATA-3 and the initiation and extent of Th2 cell differentiation. Lyn-deficient mice had a marked basophilia, a constitutive Th2 cell skewing that was exacerbated upon in vivo challenge of basophils, produced antibodies to a normally inert antigen, and failed to appropriately respond to a Th1 cell-inducing pathogen. The Th2 cell skewing was dependent on basophils, immunoglobulin E, and interleukin-4, but was independent of mast cells. Our findings demonstrate that basophil-expressed Lyn kinase exerts regulatory control on Th2 cell differentiation and function.

引用

页码：533 / 543

页数：11

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