title: Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction.
abstract: CD4(+) T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3(+) regulatory T cell fates, the role of the T-bet-related transcription factor eomesodermin (Eomes) in CD4(+) T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4(+) T lymphocytes. We find that Eomes is readily expressed in activated CD4(+) Th1 T cells in vivo. Eomes(+) CD4(+) T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4(+) T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3(+) cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4(+) T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4(+) T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4(+) T cells. This enhanced capacity of Eomes-deficient CD4(+) T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3(+) cells. Our data identify a novel role for Eomes in CD4(+) T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis.
authors.affiliation: Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, D-79104 Freiburg, Germany;
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Lupar
authors.affiliation: Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany;
authors.forename: Maria
authors.initials: M
authors.lastname: Brack
authors.affiliation: INSERM, U1043, Toulouse, F-31300, France; Centre National de la Recherche Scientifique, U5282, Toulouse, F-31300, France; Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France;
authors.forename: Laure
authors.initials: L
authors.lastname: Garnier
authors.affiliation: INSERM, U1043, Toulouse, F-31300, France; Centre National de la Recherche Scientifique, U5282, Toulouse, F-31300, France; Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France;
authors.forename: Sophie
authors.initials: S
authors.lastname: Laffont
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, D-79104 Freiburg, Germany;
authors.forename: Katharina S
authors.initials: KS
authors.lastname: Rauch
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany;
authors.forename: Kristina
authors.initials: K
authors.lastname: Schachtrup
authors.affiliation: University Medical Centre, Renal Department, Centre for Clinical Research, D-79106 Freiburg, Germany; BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University, D-79104 Freiburg, Germany; and Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, D-79102 Freiburg, Germany.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Arnold
authors.affiliation: INSERM, U1043, Toulouse, F-31300, France; Centre National de la Recherche Scientifique, U5282, Toulouse, F-31300, France; Université de Toulouse, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France;
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Guéry
authors.affiliation: Max-Planck-Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany; Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Germany; izcue@ie-freiburg.mpg.de.
authors.forename: Ana
authors.initials: A
authors.lastname: Izcue
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020825:T-Box Domain Proteins / Q000235:genetics / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: C491198:Eomes protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020825:T-Box Domain Proteins; D007371:Interferon-gamma