title: PTPN22 inhibition resets defective human central B cell tolerance.
abstract: The1858T protein tyrosine phosphatase nonreceptor type 22(PTPN22 T) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that thePTPN22 Tallele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele. In contrast, the inhibition of either PTPN22 enzymatic activity or its expression by RNA interference restored defective central B cell tolerance in this model. Thus, PTPN22 blockade may represent a therapeutic strategy for the prevention or treatment of autoimmunity.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Schickel
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kuhny
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Baldo
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Bannock
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Massad
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Haowei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Katz
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Oe
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Menard
authors.affiliation: CNRS UPR 3572, Laboratory of Immunopathology and Therapeutic Chemistry/Laboratory of Excellence Medalis, Molecular and Cellular Biology Institute (IBMC), Strasbourg, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Soulas-Sprauel
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Flavell
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Meffre