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PTPN22 inhibition resets defective human central B cell tolerance.

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 ? 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.

SUBMITTER: Schickel JN

PROVIDER: S-EPMC5127630 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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PTPN22 inhibition resets defective human central B cell tolerance.

Schickel Jean-Nicolas JN Kuhny Marcel M Baldo Alessia A Bannock Jason M JM Massad Christopher C Wang Haowei H Katz Nathan N Oe Tyler T Menard Laurence L Soulas-Sprauel Pauline P Strowig Till T Flavell Richard R Meffre Eric E

Science immunology 20160722 1

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) mi ...[more]

PMID: 27917411

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