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Article Dans Une Revue Science Immunology Année : 2016

PTPN22 inhibition resets defective human central B cell tolerance

Résumé

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.

Domaines

Immunologie

Dates et versions

hal-03653641 , version 1 (27-04-2022)

Identifiants

Citer

Jean-Nicolas Schickel, Marcel Kuhny, Alessia Baldo, Jason M Bannock, Christopher Massad, et al.. PTPN22 inhibition resets defective human central B cell tolerance. Science Immunology, 2016, 1 (1), ⟨10.1126/sciimmunol.aaf7153⟩. ⟨hal-03653641⟩
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