title: Aiolos promotes TH17 differentiation by directly silencing Il2 expression.
abstract: CD4(+) interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are instrumental in the immune response to pathogens. However, an overactive T(H)17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of T(H)17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during T(H)7 differentiation is not understood. Here we report that under T(H)17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting T(H)17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of T(H)17 cells that actively limits IL-2 production and promotes their differentiation.
authors: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. fquintana@rics.bwh.harvard.edu
authors: Francisco J
authors: FJ
authors: Quintana
authors: Hulin
authors: H
authors: Jin
authors: Evan J
authors: EJ
authors: Burns
authors: Meghan
authors: M
authors: Nadeau
authors: Ada
authors: A
authors: Yeste
authors: Deepak
authors: D
authors: Kumar
authors: Manu
authors: M
authors: Rangachari
authors: Chen
authors: C
authors: Zhu
authors: Sheng
authors: S
authors: Xiao
authors: John
authors: J
authors: Seavitt
authors: Katia
authors: K
authors: Georgopoulos
authors: Vijay K
authors: VK
authors: Kuchroo
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology; D005786:Gene Expression Regulation; D051740:Ikaros Transcription Factor; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051740:Ikaros Transcription Factor; D007371:Interferon-gamma; D007376:Interleukin-2; D018336:Receptors, Aryl Hydrocarbon; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; C484722:Ahr protein, mouse; C491396:Ikzf3 protein, mouse; C494087:Stat3 protein, mouse