title: Eos Is Redundant for Regulatory T Cell Function but Plays an Important Role in IL-2 and Th17 Production by CD4+ Conventional T Cells.
abstract: Eos belongs to the Ikaros family of transcription factors. It was reported to be a regulatory T cell (Treg) signature gene, to play a critical role in Treg suppressor functions, and to maintain Treg stability. We used mice with a global deficiency in Eos to re-examine the role of Eos expression in both Tregs and conventional T cells (Tconvs). Tregs from Eos-deficient (Eos(-/-)) mice developed normally, displayed a normal Treg phenotype, and exhibited normal suppressor function in vitro. Eos(-/-) Tregs were as effective as Tregs from wild-type (WT) mice in suppressing inflammation in a model of inflammatory bowel disease. Bone marrow (BM) from Eos(-/-) mice was as effective as that from WT mice in controlling T cell activation when used to reconstitute immunodeficient mice in the presence of scurfy fetal liver cells. Surprisingly, Eos was expressed in activated Tconvs and was required for IL-2 production, CD25 expression, and proliferation in vitro by CD4(+) Tconvs. Eos(-/-) mice developed more severe experimental autoimmune encephalomyelitis than WT mice, displayed increased numbers of effector T cells in the periphery and CNS, and amplified IL-17 production. In conclusion, our studies are not consistent with a role for Eos in Treg development and function but demonstrate that Eos plays an important role in the activation and differentiation of Tconvs.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and.
authors.forename: Sadiye Amcaoglu
authors.initials: SA
authors.lastname: Rieder
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and.
authors.forename: Amina
authors.initials: A
authors.lastname: Metidji
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and.
authors.forename: Deborah Dacek
authors.initials: DD
authors.lastname: Glass
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Thornton
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Cutaneous Biology Research Center, Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Morgan
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and eshevach@niaid.nih.gov.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Shevach
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020381:Interleukin-17; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D009419:Nerve Tissue Proteins; C118760:Zfpn1a4 protein, mouse