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

@article{citeulike:3996530, abstract = {In the course of infection or autoimmunity, particular transcription factors orchestrate the differentiation of TH1, TH2 or TH17 effector cells, the responses of which are limited by a distinct lineage of suppressive regulatory T cells (Treg). Treg 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 TH1 and TH2 cytokine production. 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. Here we show that in mouse Treg cells, high amounts of interferon regulatory factor-4 (IRF4), a transcription factor essential for TH2 effector cell differentiation, is dependent on Foxp3 expression. We proposed that IRF4 expression endows Treg cells with the ability to suppress TH2 responses. Indeed, ablation of a conditional Irf4 allele in Treg cells resulted in selective dysregulation of TH2 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 Treg cells. Our results indicate that Treg 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.}, author = {Zheng, Ye and Chaudhry, Ashutosh and Kas, Arnold and Deroos, Paul and Kim, Jeong M. and Chu, Tin-Tin and Corcoran, Lynn and Treuting, Piper and Klein, Ulf and Rudensky, Alexander Y.}, citeulike-article-id = {3996530}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07674}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19182775}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19182775}, day = {01}, doi = {10.1038/nature07674}, issn = {0028-0836}, journal = {Nature}, keywords = {transcriptionfactor, treg}, month = {February}, posted-at = {2009-02-25 22:54:59}, priority = {5}, publisher = {Nature Publishing Group}, title = {Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses}, url = {http://dx.doi.org/10.1038/nature07674}, year = {2009} }

TY - JOUR ID - citeulike:3996530 L3 - citeulike-article-id:3996530 N2 - In the course of infection or autoimmunity, particular transcription factors orchestrate the differentiation of TH1, TH2 or TH17 effector cells, the responses of which are limited by a distinct lineage of suppressive regulatory T cells (Treg). Treg 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 TH1 and TH2 cytokine production. 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. Here we show that in mouse Treg cells, high amounts of interferon regulatory factor-4 (IRF4), a transcription factor essential for TH2 effector cell differentiation, is dependent on Foxp3 expression. We proposed that IRF4 expression endows Treg cells with the ability to suppress TH2 responses. Indeed, ablation of a conditional Irf4 allele in Treg cells resulted in selective dysregulation of TH2 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 Treg cells. Our results indicate that Treg 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. JF - Nature SN - 0028-0836 TI - Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses PB - Nature Publishing Group KW - transcriptionfactor KW - treg AU - Zheng, Ye AU - Chaudhry, Ashutosh AU - Kas, Arnold AU - Deroos, Paul AU - Kim, Jeong AU - Chu, Tin-Tin AU - Corcoran, Lynn AU - Treuting, Piper AU - Klein, Ulf AU - Rudensky, Alexander PY - 2009/02/01/ UR - http://dx.doi.org/10.1038/nature07674 ER -