Details

Autor(en) / Beteiligte

• YE ZHENG
• CHAUDHRY, Ashutosh
• KAS, Arnold
• DEROOS, Paul
• KIM, Jeong M
• CHU, Tin-Tin
• CORCORAN, Lynn
• TREUTING, Piper
• KLEIN, Ulf
• RUDENSKY, Alexander Y

Titel

Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses

Ist Teil von

• Nature (London), 2009-02, Vol.458 (7236), p.351-356

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2009

Link zum Volltext

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• 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.