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Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses
Jinfang Zhu1, Booki Min, Jane Hu-Li
1Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jfzhu@niaid.nih.gov <jfzhu@niaid.nih.gov>
Nature Immunology
|October 12, 2004
Summary
The transcription factor GATA-3 is crucial for T helper type 2 (T(H)2) cell differentiation. Genetic deletion of GATA-3 impairs T(H)2 development and promotes T(H)1 responses, acting as a key switch.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- The transcription factor GATA-3 is linked to T helper type 2 (T(H)2) cell differentiation.
- Genetic evidence for GATA-3's role in T(H)2 differentiation has been limited.
Purpose of the Study:
- To investigate the necessity of GATA-3 in T(H)2 cell differentiation and function.
- To determine if GATA-3 acts as a switch between T(H)1 and T(H)2 cell fates.
Main Methods:
- Generation of a conditional GATA-3-deficient mouse line.
- In vitro and in vivo deletion of the Gata3 gene.
- Analysis of T(H)1 and T(H)2 cell differentiation, cytokine production, and cell growth.
- Infection model (Nippostrongylus brasiliensis) to assess in vivo T(H)2 responses.
Main Results:
- Gata3 deletion in vitro diminished both IL-4-dependent and independent T(H)2 differentiation.
- Gata3 deletion promoted T(H)1 differentiation in the absence of IL-12 and IFN-gamma.
- Gata3 deletion limited T(H)2 cell growth but not T(H)1 cell growth.
- In vivo Gata3 deletion abolished T(H)2 responses and permitted IFN-gamma production during parasitic infection.
- Deletion of Gata3 from established T(H)2 cells abolished IL-5 and IL-13 production.
Conclusions:
- GATA-3 is essential for T(H)2 cell differentiation and function.
- GATA-3 acts as a principal regulator, switching the balance between T(H)1 and T(H)2 cell responses.
- GATA-3 controls the production of key T(H)2 cytokines IL-5 and IL-13.