title: Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses.
abstract: The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite (HDM) challenge without affecting cytotoxic T lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus, Toxoplasma gondii, and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland. Electronic address: r.tussiwand@unibas.ch.
authors.forename: Roxane
authors.initials: R
authors.lastname: Tussiwand
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, the Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Everts
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Grajales-Reyes
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Kretzer
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Arifumi
authors.initials: A
authors.lastname: Iwata
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, 1 Children's Place, St. Louis, MO 63110, USA.
authors.forename: Juhi
authors.initials: J
authors.lastname: Bagaitkar
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wong
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Anderson
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: kmurphy@wustl.edu.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001249:Asthma / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000276:immunology; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D039981:Pyroglyphidae; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
chemical_list: D000947:Antigens, Helminth; D050835:Interferon Regulatory Factors; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D000099218:Interferon Regulatory Factor-4; C000715468:Klf4 protein, mouse