title: Enforced ROR(gamma)t expression in haematopoietic stem cells increases regulatory T cell number, which reduces immunoreactivity and attenuates hypersensitivity in vivo.
abstract: BACKGROUND
  The retinoic acid receptor-related orphan receptor gammat (ROR(gamma)t) is a key transcription factor involved in the generation of T-helper 17 (Th17) cells, which mediate tissue inflammation and autoimmunity. However, recent studies indicated that less than half of all ROR(gamma)t(+) Talphabeta cells express IL-17, while the others are Foxp3(+) Talphabeta cells expressing IL-10. These observations raise questions regarding the role of ROR(gamma)t in the early differentiation process of T cells from haematopoietic stem cells.
  
  
  METHODS
  To examine the role of RORyt in T cell differentiation, mice were reconstituted with ROR(gamma)t cDNA-transduced haematopoietic stem cells and the role of ROR(gamma)t in T cell differentiation was studied in a mouse bone marrow transplantation model in vivo.
  
  
  RESULTS
  While the number of Th17 cells increased with the reduction in Thl cell number in transplanted mice, peripheral blood Foxp3(+) Talphabeta cell number also increased, which attenuated the severity of contact hypersensitivity on skin exposed to 2,4-dinitrofluorobenzene. The number of non-transduced Foxp3(+) regulatory T cells (Treg cells) also increased in these mice.
  
  
  CONCLUSIONS
  These observations suggest that the enforced expression of ROR(gamma)t in haematopoietic stem cells induces differentiation of Thl7 cells and results in an increase in Foxp3(+) Treg cell number to limit self-tissue damage.
authors.affiliation: Department of Dermatology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nabekura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006410:Hematopoiesis / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics* / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3