title: Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation.
abstract: The differentiation of helper T cells into effector subsets is critical to host protection. Transcription factors of the E-protein and Id families are important arbiters of T cell development, but their role in the differentiation of the TH1 and TFH subsets of helper T cells is not well understood. Here, TH1 cells showed more robust Id2 expression than that of TFH cells, and depletion of Id2 via RNA-mediated interference increased the frequency of TFH cells. Furthermore, TH1 differentiation was blocked by Id2 deficiency, which led to E-protein-dependent accumulation of effector cells with mixed characteristics during viral infection and severely impaired the generation of TH1 cells following infection with Toxoplasma gondii. The TFH cell-defining transcriptional repressor Bcl6 bound the Id2 locus, which provides a mechanism for the bimodal Id2 expression and reciprocal development of TH1 cells and TFH cells.
authors.affiliation: Department of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Shaw
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Bélanger
authors.affiliation: Department of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: Kyla D
authors.initials: KD
authors.lastname: Omilusik
authors.affiliation: Department of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: Sunglim
authors.initials: S
authors.lastname: Cho
authors.affiliation: Division of Signaling and Gene Expression, La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Scott-Browne
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.
authors.forename: J Philip
authors.initials: JP
authors.lastname: Nance
authors.affiliation: Department of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: John
authors.initials: J
authors.lastname: Goulding
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lasorella
authors.affiliation: Department of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Lu
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.|Department of Medicine, University of California San Diego, La Jolla, California, USA.
authors.forename: Shane
authors.identifier: 0000-0002-6484-6262
authors.initials: S
authors.lastname: Crotty
authors.affiliation: Department of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D018858:Germinal Center / Q000276:immunology; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011485:Protein Binding; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018417:Th1 Cells / Q000469:parasitology / Q000502:physiology* / Q000821:virology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051797:Inhibitor of Differentiation Protein 2; D051560:Proto-Oncogene Proteins c-bcl-6; D034741:RNA, Small Interfering; C490010:Bcl6 protein, mouse; C497452:Idb2 protein, mouse; C075668:Tcf3 protein, mouse