PTPN22 inhibition resets defective human central B cell tolerance
PTPN22 inhibition resets defective human central B cell tolerance
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DOI：
10.1126/sciimmunol.aaf7153
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发表时间：
2016-07-01
影响因子：
24.8
通讯作者：
Meffre, Eric
中科院分区：
文献类型：
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作者：
Schickel, Jean-Nicolas;Kuhny, Marcel;Meffre, Eric
1858T蛋白酪氨酸磷酸酶非受体22型（PTPN22）等位基因是与许多自身免疫性疾病相关的主要危险因素之一，并与人类自身反应性B细胞的缺陷清除相关。为了确定抑制PTPN22是否有利于消除自身反应性B细胞，我们首先使用nod -scid共同y链敲除（NSG）小鼠移植表达该等位基因的人造血干细胞，证明PTPN22 T等位基因干扰了中央B细胞耐受性的建立。相反，在该模型中，通过RNA干扰抑制PTPN22酶活性或其表达可恢复有缺陷的中央B细胞耐受性。因此，PTPN22阻断可能是预防或治疗自身免疫的一种治疗策略。
The 1858T protein tyrosine phosphatase nonreceptor type 22 (PTPN22 1) 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 y 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.