title: The transcription factors Thpok and LRF are necessary and partly redundant for T helper cell differentiation.
abstract: T helper (Th) cells are critical for defenses against infection and recognize peptides bound to class II major histocompatibility complex (MHC II) molecules. Although transcription factors have been identified that direct Th cells into specific effector fates, whether a "master" regulator controls the developmental program common to all Th cells remains unclear. Here, we showed that the two transcription factors Thpok and LRF share this function. Although disruption of both factors did not prevent the generation of MHC II-specific T cells, these cells failed to express Th cell genes or undergo Th cell differentiation in vivo. In contrast, T cells lacking Thpok, which only displayed LRF-dependent functions, contributed to multiple effector responses, both in vitro and in vivo, with the notable exception of Th2 cell responses that control extracellular parasites. These findings identify the Thpok-LRF pair as a core node of Th cell differentiation and function.
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Carpenter
authors.forename: John R
authors.initials: JR
authors.lastname: Grainger
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xiong
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: H Hamlet
authors.initials: HH
authors.lastname: Chu
authors.forename: Lie
authors.initials: L
authors.lastname: Wang
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.forename: Liliane
authors.initials: L
authors.lastname: dos Santos
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Marc K
authors.initials: MK
authors.lastname: Jenkins
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Rémy
authors.initials: R
authors.lastname: Bosselut
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology*; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000172:deficiency / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497211:Zbtb7b protein, mouse; C117093:Zbtb7a protein, mouse