Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses
- Author(s)
- Zheng, Y; Chaudhry, A; Kas, A; deRoos, P; Kim, JM; Chu, TT; Corcoran, L; Treuting, P; Klein, U; Rudensky, AY;
- Details
- Publication Year 2009-03-19,Volume 458,Issue #7236,Page 351-U116
- Journal Title
- NATURE
- Publication Type
- Journal Article
- Abstract
- In the course of infection or autoimmunity, particular transcription factors orchestrate the differentiation of T(H)1, T(H)2 or T(H)17 effector cells, the responses of which are limited by a distinct lineage of suppressive regulatory T cells (T-reg). T-reg cell differentiation and function are guided by the transcription factor Foxp3, and their deficiency due to mutations in Foxp3 results in aggressive fatal autoimmune disease associated with sharply augmented T(H)1 and T(H)2 cytokine production(1-3). Recent studies suggested that Foxp3 regulates the bulk of the Foxp3-dependent transcriptional program indirectly through a set of transcriptional regulators serving as direct Foxp3 targets(4,5). Here we show that in mouse T-reg cells, high amounts of interferon regulatory factor-4 (IRF4), a transcription factor essential for T(H)2 effector cell differentiation, is dependent on Foxp3 expression. We proposed that IRF4 expression endows T-reg cells with the ability to suppress T(H)2 responses. Indeed, ablation of a conditional Irf4 allele in T-reg cells resulted in selective dysregulation of T(H)2 responses, IL4-dependent immunoglobulin isotype production, and tissue lesions with pronounced plasma cell infiltration, in contrast to the mononuclear-cell-dominated pathology typical of mice lacking T-reg cells. Our results indicate that T-reg cells use components of the transcriptional machinery, promoting a particular type of effector CD4(+) T cell differentiation, to efficiently restrain the corresponding type of the immune response.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- SELF-TOLERANCE; TARGET GENES; DIFFERENTIATION; FOXP3; LINEAGE; TH2; INTERLEUKIN-10; ADENOSINE; DISEASE; ABSENCE
- Publisher's Version
- https://doi.org/10.1038/nature07674
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2009-03-19 12:00:00