title: Signal transducer and activator of transcription 3 (Stat3) contributes to T-cell homeostasis by regulating pro-survival Bcl-2 family genes.
abstract: The naive T-cell pool in peripheral lymphoid tissues is fairly stable in terms of number, diversity and functional capabilities in spite of the absence of prominent stimuli. This stability is attributed to continuous tuning of the composition of the T-cell pool by various homeostatic signals. Despite extensive research into the link between signal transducer and activator of transcription 3 (Stat3) and T-cell survival, little is known about how Stat3 regulates homeostasis by maintaining the required naive T-cell population in peripheral lymphoid organs. We assessed whether the elimination of Stat3 in T cells limits T-cell survival. We demonstrated that the proportion and number of single-positive thymocytes as well as T cells in the spleen and lymph nodes were significantly decreased in the Stat3-deficient group as a result of the enhanced susceptibility of Stat3-deleted T lymphocytes to apoptosis. Importantly, expression of the anti-apoptotic Bcl-2 and Bcl-xL was markedly decreased in Stat3-deleted single-positive thymocytes and T lymphocytes, suggesting that Stat3 helps to maintain the T-cell pool in the resting condition by promoting the expression of Bcl-2 family genes. These findings suggest the importance of Stat3 in the integration of homeostatic cues for the maintenance and functional tuning of the T-cell pool.
authors.affiliation: Department of Pharmacology and Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischaemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Neuro-Immune Information Storage Network Research Centre, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jin-Ku
authors.initials: JK
authors.lastname: Lee
authors.forename: Cheolhee
authors.initials: C
authors.lastname: Won
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Yi
authors.forename: Seung-Hyeok
authors.initials: SH
authors.lastname: Seok
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.forename: Sang-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Chung
authors.forename: Hyun Gyu
authors.initials: HG
authors.lastname: Lee
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; D051020:bcl-X Protein
keywords: Bcl-2; Stat3; T cell; apoptosis; homeostasis