Lyn kinase controls basophil GATA-3 transcription factor expression and induction of Th2 cell differentiation.
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.
Laboratory of Immune Cell Signaling, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.
Nicolas
N
Charles
Wendy T
WT
Watford
Haydeé L
HL
Ramos
Lars
L
Hellman
Hans C
HC
Oettgen
Gregorio
G
Gomez
John J
JJ
Ryan
John J
JJ
O'Shea
Juan
J
Rivera
D000818:Animals; D001491:Basophils / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology*; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D050990:GATA3 Transcription Factor; D015847:Interleukin-4; D007073:Immunoglobulin E; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases