PTPN22 inhibition resets defective human central B cell tolerance

The ( ) 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 allele i...

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Published inScience immunology Vol. 1; no. 1; p. aaf7153
Main Authors Schickel, Jean-Nicolas, Kuhny, Marcel, Baldo, Alessia, Bannock, Jason M, Massad, Christopher, Wang, Haowei, Katz, Nathan, Oe, Tyler, Menard, Laurence, Soulas-Sprauel, Pauline, Strowig, Till, Flavell, Richard, Meffre, Eric
Format Journal Article
LanguageEnglish
Published United States 22.07.2016
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Summary:The ( ) 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 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.
ISSN:2470-9468