Indispensable role of Stat5a in Stat6-independent Th2 cell differentiation and allergic airway inflammation.
It is well-recognized that Stat6 plays a critical role in Th2 cell differentiation and the induction of allergic inflammation. We have previously shown that Stat5a is also required for Th2 cell differentiation and allergic airway inflammation. However, it is the relative importance and redundancy of Stat6 and Stat5a in Th2 cell differentiation and allergic airway inflammation are unknown. In this study we addressed these issues by comparing Stat5a-deficient (Stat5a(-/-)) mice, Stat6(-/-) mice, and Stat5a- and Stat6 double-deficient (Stat5a(-/-) Stat6(-/-)) mice on the same genetic background. Th2 cell differentiation was severely decreased in Stat6(-/-)CD4+ T cells, but Stat6-independent Th2 cell differentiation was still significantly observed in Stat6(-/-)CD4+ T cells. However, even in the Th2-polarizing condition (IL-4 plus anti-IFN-gamma mAb), no Th2 cells developed in Stat5a(-/-)Stat6(-/-) CD4+ T cells. Moreover, Ag-induced eosinophil and lymphocyte recruitment in the airways was severely decreased in Stat5a(-/-)Stat6(-/-) mice compared with that in Stat6(-/-) mice. These results indicate that Stat5a plays an indispensable role in Stat6-independent Th2 cell differentiation and subsequent Th2 cell-mediated allergic airway inflammation.
Takatori
Hiroaki
H
Department of Allergy and Clinical Immunology, Chiba University School of Medicine, Chiba, Japan.
Nakajima
Hiroshi
H
Hirose
Koichi
K
Kagami
Shin-ichiro
S
Tamachi
Tomohiro
T
Suto
Akira
A
Suzuki
Kotaro
K
Saito
Yasushi
Y
Iwamoto
Itsuo
I
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; C494093:Stat5a protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D010047:Ovalbumin