title: Ets-1 maintains IL-7 receptor expression in peripheral T cells.
abstract: The expression of CD127, the IL-7-binding subunit of the IL-7 R, is tightly regulated during the development and activation of T cells and is reduced during chronic viral infection. However, the molecular mechanism regulating the dynamic expression of CD127 is still poorly understood. In this study, we report that the transcription factor Ets-1 is required for maintaining the expression of CD127 in murine peripheral T cells. Ets-1 binds to and activates the CD127 promoter, and its absence leads to reduced CD127 expression, attenuated IL-7 signaling, and impaired IL-7-dependent homeostatic proliferation of T cells. The expression of CD127 and Ets-1 is strongly correlated in human T cells. Both CD127 and Ets-1 expression are decreased in CD8(+) T cells during HIV infection. In addition, HIV-associated loss of CD127 is only observed in Ets-1(low) effector memory and central memory but not in Ets-1(high) naive CD8(+) T cells. Taken together, our data identify Ets-1 as a critical regulator of CD127 expression in T cells.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Grenningloh
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Tai
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Tomoyuki C
authors.initials: TC
authors.lastname: Hongo
authors.forename: Adam T
authors.initials: AT
authors.lastname: Chicoine
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Ho
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D050784:Proto-Oncogene Protein c-ets-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
chemical_list: C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; C508605:IL7 protein, human; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D050784:Proto-Oncogene Protein c-ets-1