title: TRAF6 directs commitment to regulatory T cells in thymocytes.
abstract: Regulatory T cells (Tregs), a subset of CD4(+) helper T cells, are crucial for immunological self-tolerance. Defect in development or function of Tregs results in autoimmune disease in human and mice. Whereas it is known that Tregs mainly develop in the thymus, the molecular mechanism underlying development of Treg is not fully understood. TRAF6-deficient mice showed a severe defect in the Treg development in thymus. In vitro fetal thymic organ culture experiments indicated that the defect is ascribed to the absence of TRAF6 in thymic cells. Moreover, mixed fetal liver transfer experiments revealed that the development of Foxp3(+) cells differentiated from Traf6(-/-) hematopoietic cells was specifically impaired in the thymus, indicating cell-intrinsic requirement for TRAF6 in the Treg development. On the other hand, TRAF6 is not required for the development of conventional CD4(+) T cell. In addition, TGFβ-dependent induction of Foxp3 in CD4(+) T cells in vitro was not impaired by the absence of TRAF6. Overall, our data indicate that TRAF6 plays an essential role on the commitment of immature thymocytes to thymic Tregs in cell-intrinsic fashion.
authors.affiliation: Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shimo
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yanai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ohshima
authors.forename: Junwen
authors.initials: J
authors.lastname: Qin
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Motegi
authors.forename: Yuya
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Shohei
authors.initials: S
authors.lastname: Hori
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Inoue
authors.forename: Taishin
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000502:physiology*; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D048029:TNF Receptor-Associated Factor 6; D016212:Transforming Growth Factor beta