Exosomes Derived from T Lymphocytes Enhance Expression of CXCL10 Induced By IFN-γin Rheumatoid Arthritis Synovial Fibroblasts Via Pattern Recognition Receptor, RIG-I

Kunihiko Umekita, Shunichi Miyauchi, Koshou Iwao, Mao Rikitake, Yuuki Rikitake, Chihiro Kawada, Ayako Aizawa, Yumi Kariya, Motohiro Matsuda, Takeshi Kawaguchi, Hajime Nomura, Ichiro Takajo and Akihiko Okayama, Department of Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Inflammation, innate immunity and rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 7, 2017

Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Exosomes have been recognized to have a function in cell-to-cell communication by transporting various factors including proteins and nucleic acids. These factors impact cell viability and cell differentiation, and are likely to play a prominent role in the pathophysiology of rheumatoid arthritis (RA); however, it is still not reveal that the roles of exosomes as inflammatory mediator in pathogenesis of RA. The purpose of this study is to investigate the role of T lymphocytes derived exosomes in the pathogenesis of RA.

Methods: Exosomes were isolated and purified from cultured medium of T lymphocytes cell line (JK). RA synovial fibroblasts (RASFs) were cultured with exosomes derived from JK with or without IFN-gamma for 24hours. Total RNA was extracted using TRIZOL methods. The expression of RIG-I, TLR3, IL-6 and CXCL10 mRNA in RASFs was measured using real-time quantitative PCR. The protein levels of RIG-I and TLR3 were determined by immune blotting. Silencing of RIG-I and TLR3 in RASF was performed by transfection of siRNA against these proteins.

Results: Treatment with PMA/Ionomycin increased the release of exosomes from JK. Large amount of RNA was detectable in exosomes derived from JK. Exosomes derived from JK increased the expression of IL-6 and CXCL10 mRNA in RASFs. When IFN-gamma is added to the culture medium of RASFs, increased expression of both RIG-I and TLR3 protein in RASF was observed in a dose dependent manner. IFN-gamma also induced the expression of CXCL10 mRNA, but not IL-6 mRNA, in RASF. Exosomes derived from JK significantly enhances the expression of CXCL10 mRNA, but not IL-6 mRNA, in RASF treated with IFN-gamma. Finally, silencing of RIG-I, but not TLR3, suppressed the expression of CXCL10 in RASF induced by co-stimulation of both exosomes and IFN-gamma.

Conclusion: The present study demonstrates that exosomes derived from JK enhance IFN-gamma induced expression of CXCL10 in RASF via pattern recognition receptor, RIG-I. The interaction between exosomes derived from T-cells and RIG-I can be a therapeutic target for RA.

Disclosure: K. Umekita, None; S. Miyauchi, None; K. Iwao, None; M. Rikitake, None; Y. Rikitake, None; C. Kawada, None; A. Aizawa, None; Y. Kariya, None; M. Matsuda, None; T. Kawaguchi, None; H. Nomura, None; I. Takajo, None; A. Okayama, None.

To cite this abstract in AMA style:

Umekita K, Miyauchi S, Iwao K, Rikitake M, Rikitake Y, Kawada C, Aizawa A, Kariya Y, Matsuda M, Kawaguchi T, Nomura H, Takajo I, Okayama A. Exosomes Derived from T Lymphocytes Enhance Expression of CXCL10 Induced By IFN-γin Rheumatoid Arthritis Synovial Fibroblasts Via Pattern Recognition Receptor, RIG-I [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/exosomes-derived-from-t-lymphocytes-enhance-expression-of-cxcl10-induced-by-ifn-%ce%b3in-rheumatoid-arthritis-synovial-fibroblasts-via-pattern-recognition-receptor-rig-i/. Accessed .

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