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Sci Immunol. 2016;1(1). pii: aaf7153. Epub 2016 Jul 22.

PTPN22 inhibition resets defective human central B cell tolerance.

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA.
2
CNRS UPR 3572, Laboratory of Immunopathology and Therapeutic Chemistry/Laboratory of Excellence Medalis, Molecular and Cellular Biology Institute (IBMC), Strasbourg, France.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.

Abstract

The 1858T 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 the PTPN22 T allele 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.

PMID:
27917411
PMCID:
PMC5127630
[Available on 2017-07-22]
DOI:
10.1126/sciimmunol.aaf7153
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