title: Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells.
abstract: Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN) in response to viruses. The IFN-producing capacity of pDCs is regulated by specific inhibitory receptors, yet none of the known receptors are conserved in evolution. We report that within the human immune system, receptor protein tyrosine phosphatase sigma (PTPRS) is expressed specifically on pDCs. Surface PTPRS was rapidly downregulated after pDC activation, and only PTPRS(-) pDCs produced IFN-α. Antibody-mediated PTPRS crosslinking inhibited pDC activation, whereas PTPRS knockdown enhanced IFN response in a pDC cell line. Similarly, murine Ptprs and the homologous receptor phosphatase Ptprf were specifically co-expressed in murine pDCs. Haplodeficiency or DC-specific deletion of Ptprs on Ptprf-deficient background were associated with enhanced IFN response of pDCs, leukocyte infiltration in the intestine and mild colitis. Thus, PTPRS represents an evolutionarily conserved pDC-specific inhibitory receptor, and is required to prevent spontaneous IFN production and immune-mediated intestinal inflammation.
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Bunin
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Vanja
authors.initials: V
authors.lastname: Sisirak
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Hiyaa S
authors.initials: HS
authors.lastname: Ghosh
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Lucja T
authors.initials: LT
authors.lastname: Grajkowska
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Z Esther
authors.initials: ZE
authors.lastname: Hou
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Miron
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Cliff
authors.initials: C
authors.lastname: Yang
authors.affiliation: Lymphoid Malignancy Branch, Center for Cancer Research, National Cancer Institute, Rockville, MD 20852, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Ceribelli
authors.affiliation: Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Noriko
authors.initials: N
authors.lastname: Uetani
authors.affiliation: R&D Laboratory, EFS Rhone-Alpes Grenoble, La Tronche F-38701, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Chaperot
authors.affiliation: R&D Laboratory, EFS Rhone-Alpes Grenoble, La Tronche F-38701, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Plumas
authors.affiliation: Department of Cell Biology, Radboud University, 6525 GA Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Wiljan
authors.initials: W
authors.lastname: Hendriks
authors.affiliation: Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Häcker
authors.affiliation: Lymphoid Malignancy Branch, Center for Cancer Research, National Cancer Institute, Rockville, MD 20852, USA.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.affiliation: Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Green
authors.affiliation: Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: boris.reizis@nyumc.org.
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D007371:Interferon-gamma; C516883:PTPRS protein, human; C000709129:Ptprf protein, mouse; C516885:Ptprs protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2