The Autoimmunity-Associated Gene PTPN22 Potentiates Toll-like Receptor-Driven, Type 1 Interferon-Dependent Immunity

Yaya Wang, Iftach Shaked, Stephanie M. Stanford, Wenbo Zhou, Julie M. Curtsinger, Zbigniew Mikulski, Zachary R. Shaheen, Genhong Cheng, Kristy Sawatzke, Amanda M. Campbell, Jennifer L. Auger, Hatice Bilgic, Fernanda M. Shoyama, David O. Schmeling, Henry H. Balfour, Kiminori Hasegawa, Andrew C. Chan, John A. Corbett, Bryce A. Binstadt, Matthew F. MescherKlaus Ley, Nunzio Bottini, Erik J. Peterson

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

166 اقتباسات (Scopus)

ملخص

Immune cells sense microbial products through Toll-like receptors (TLR), which trigger host defense responses including type 1 interferons (IFNs) secretion. A coding polymorphism in the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is a susceptibility allele for human autoimmune and infectious disease. We report that Ptpn22 selectively regulated type 1 IFN production after TLR engagement in myeloid cells. Ptpn22 promoted host antiviral responses and was critical for TLR agonist-induced, type 1 IFN-dependent suppression of inflammation in colitis and arthritis. PTPN22 directly associated with TNF receptor-associated factor 3 (TRAF3) and promotes TRAF3 lysine 63-linked ubiquitination. The disease-associated PTPN22W variant failed to promote TRAF3 ubiquitination, type 1 IFN upregulation, and type 1 IFN-dependent suppression of arthritis. The findings establish a candidate innate immune mechanism of action for a human autoimmunity "risk" gene in the regulation of host defense and inflammation.

اللغة الأصليةالإنجليزيّة
الصفحات (من إلى)111-122
عدد الصفحات12
دوريةImmunity
مستوى الصوت39
رقم الإصدار1
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 25 يوليو 2013
منشور خارجيًانعم

بصمة

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