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IgG Immunocomplexes Sensitize Human Monocytes for Inflammatory Hyperactivity via Transcriptomic and Epigenetic Reprogramming in Rheumatoid Arthritis.

Journal of immunology (Baltimore, Md. : 1950) (2018-05-02)
Qiao Zhong, Fang-Yuan Gong, Zheng Gong, Sheng-Hao Hua, Ke-Qin Zeng, Xiao-Ming Gao
ABSTRACT

Prevalence of circulating immunocomplexes (ICs) strongly correlates with rheumatoid arthritis (RA) in humans. Deposits of IgG-ICs are abundant in affected joints of patients, yet molecular mechanisms for the pathogenic roles of such ICs are not fully understood. In this study, we present evidence that IgG-ICs precipitated from RA sera sensitized human monocytes for a long-lasting inflammatory functional state, characterized by a strong TNF-α response to cellular proteins representing damage-associated molecular patterns and microbe-derived pathogen-associated molecular patterns. Importantly, plate-coated human IgG (a mimic of deposited IC without Ag restriction) exhibited a similarly robust ability of monocyte sensitization in vitro. The plate-coated human IgG-induced functional programming is accompanied by transcriptomic and epigenetic modification of various inflammatory cytokines and negative regulator genes. Moreover, macrophages freshly isolated from synovia of patients with RA, but not sera-negative arthropathy, displayed a signature gene expression profile highly similar to that of IC-sensitized human monocytes, indicative of historical priming events by IgG-ICs in vivo. Thus, the ability of IgG-ICs to drive sustainable functional sensitization/reprogramming of monocytes and macrophages toward inflammation may render them key players in the development of RA.

MATERIALS
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Brand
Product Description

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Zymosan A from Saccharomyces cerevisiae, for inducing inflamatory response
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IgM from human serum, reagent grade, ~95% (HPLC), buffered aqueous solution
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Anti-trimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit
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Polymyxin B-Agarose, aqueous glycerol suspension
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