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Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses
Ye Zheng1, Ashutosh Chaudhry, Arnold Kas
1Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Nature
|February 3, 2009
Summary
Regulatory T cells (Treg) use the transcription factor IRF4 to suppress T(H)2 immune responses. Loss of IRF4 in Treg cells selectively impairs T(H)2 suppression, leading to autoimmune pathology.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- T helper (T(H)) cells differentiate into effector subsets (T(H)1, T(H)2, T(H)17) during infection or autoimmunity.
- Regulatory T cells (T(reg)) suppress immune responses, with differentiation guided by the transcription factor Foxp3.
- Foxp3 deficiency causes severe autoimmune disease with increased T(H)1 and T(H)2 cytokines.
Purpose of the Study:
- To investigate the role of transcription factor IRF4 in T(reg) cell function.
- To determine if IRF4 is a direct Foxp3 target and mediates T(reg) suppression of T(H)2 responses.
Main Methods:
- Analysis of IRF4 expression in mouse T(reg) cells.
- Conditional ablation of the Irf4 gene in T(reg) cells.
- Assessment of T(H)2 cell responses, immunoglobulin production, and tissue pathology.
Main Results:
- Foxp3 expression is required for high IRF4 levels in mouse T(reg) cells.
- Ablation of Irf4 in T(reg) cells led to dysregulated T(H)2 responses and IL4-dependent immunoglobulin production.
- T(reg) cell-specific IRF4 deficiency resulted in distinct autoimmune pathology characterized by plasma cell infiltration.
Conclusions:
- T(reg) cells utilize IRF4 to specifically suppress T(H)2-mediated immune responses.
- This mechanism highlights how T(reg) cells co-opt effector cell differentiation machinery to control specific immune responses.
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