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Poly( ADP ‐Ribose) Polymerase Enhances Infiltration of Mononuclear Cells in Primary Sjögren's Syndrome Through Interferon‐Induced Protein With Tetratricopeptide Repeats 1–Mediated Up‐Regulation of CXCL 10
Author(s) -
Tian Qingqing,
Zhao Han,
Ling Hanzhi,
Sun Li,
Xiao Chipeng,
Yin Guoyu,
Wang Xiaobing,
Wu Gan,
Yang Chenglin,
Chen Mu,
Jin Shengwei,
Yang Xinyu,
Wang Jianguang
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41195
Subject(s) - peripheral blood mononuclear cell , poly adp ribose polymerase , microbiology and biotechnology , interferon , parp inhibitor , cd38 , cd19 , biology , chemistry , immunology , flow cytometry , polymerase , in vitro , stem cell , biochemistry , cd34 , gene
Objective Mononuclear cell infiltration and type I interferon ( IFN ) system activation play an important role in primary Sjögren's syndrome ( SS ). We undertook this study to investigate the mechanism of poly( ADP ‐ribose) polymerase family member 9 ( PARP ‐9) on mononuclear cell infiltration triggered by type I IFN . Methods A proteomic study was conducted in peripheral blood mononuclear cells from patients with primary SS (n = 30) and healthy controls (n = 30) to determine differentially expressed proteins (DEPs) ( P < 0.05; fold change >1.20). Labial salivary glands (LSGs) were isolated for hematoxylin and eosin staining and immunohistochemical analysis. CD19+ B cells were purified by magnetic cell sorting for immunofluorescence staining, lentivirus–PARP‐9 transfection, and IFNα treatment experiments. PARP‐9 small interfering RNA (siRNA) and DTX3L siRNA were delivered into female NOD/LtJ female mice to determine their effect. Results The overexpression of PARP‐9 and CXCL10 as well as their colocalization was confirmed in primary SS. PARP‐9 levels in LSGs rose with increased Chisholm scores in patients with primary SS. PARP‐9 and DTX3L were present in the infiltrating mononuclear cells from salivary glands in female NOD/LtJ mouse models. Additionally, Ingenuity Pathway Analysis networks of DEPs demonstrated that PARP‐9, STAT1, and IFN‐induced protein with tetratricopeptide repeats 1 (IFIT‐1) participated in the IFN‐related pathway. Furthermore, PARP‐9 could up‐regulate the expression of IFIT1 and CXCL10 in B cells. Moreover, PARP‐9 and CXCL10 could be induced by IFNα in B cells. Conclusion This study is the first to implicate PARP ‐9 as a regulator of infiltration of mononuclear cells in primary SS progression and to reveal that PARP ‐9 increases CXCL 10 expression through up‐regulating IFIT ‐1, which is mediated by the phosphorylation of STAT 1. PARP ‐9 might therefore be a novel therapeutic target for primary SS .