Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis.

Autor: Kam NW; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Liu D; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Cai Z; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Mak WY; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Wong CK; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Chiu KH; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Wong KY; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Tsang WL; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong., Tam LS; From the Department of Medicine and Therapeutics, and Department of Chemical Pathology, and Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Department of Orthopaedics and Traumatology, Prince of Wales Hospital; Department of Orthopaedics and Traumatology, Princess Margaret Hospital; Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. lstam@cuhk.edu.hk.; N.W. Kam, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; D. Liu, MPhil, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong; Z. Cai, PhD, Department of Chemical Pathology, The Chinese University of Hong Kong; W.Y. Mak, BSc, Department of Medicine and Therapeutics, The Chinese University of Hong Kong; C.K. Wong, PhD, Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, and Department of Chemical Pathology, The Chinese University of Hong Kong; K.H. Chiu, FRCS, Department of Orthopaedics and Traumatology, Prince of Wales Hospital; K.Y. Wong, FRCS, Department of Orthopaedics and Traumatology, Princess Margaret Hospital; W.L. Tsang, FRCS, Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital; L.S. Tam, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong. lstam@cuhk.edu.hk.
Jazyk: angličtina
Zdroj: The Journal of rheumatology [J Rheumatol] 2018 Apr; Vol. 45 (4), pp. 563-573. Date of Electronic Publication: 2017 Dec 15.
DOI: 10.3899/jrheum.161363
Abstrakt: Objective: Elevated expression of interleukin 35 (IL-35) is associated with autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the functional interaction among IL-35, B cells, and stromal cells residing in the synovium of patients with RA and osteoarthritis (OA).
Methods: IL-35 (EBI-3/p35) expression was investigated in RA and OA synovium using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. IL-35 receptor (IL-35R) expression on B cells dissociated from synovium and periphery of patients with RA, OA, and healthy donor controls (HC) was determined by flow cytometry. The degree of B cells activation after IL-4 and/or IL-35 stimulation was measured by flow cytometry and qRT-PCR. Synovial fibroblasts (SF) purified from RA and OA synovium were cocultured with peripheral HC B cells in the presence/absence of tumor necrosis factor-α (TNF-α) and with/without anti-IL-35-blocking antibodies.
Results: EBI-3/p35 transcripts were expressed in close proximity to B cells residing in RA and OA synovium. IL-35R subunits, gp130 and IL-27Rα, but not IL-12Rβ2, were expressed in B cells extracted from the synovium and periphery of patients with RA/OA. Notably, RA synovium expressed the highest level of IL-27Rα on their cell surface. IL-35 induced proliferation and IgG production in HC B cells. Cocultures of HC B cells with RASF, but not OASF, exhibited significantly elevated B cells activation. TNF-α-induced, RASF-dependent secretion of IgG in B cells is partly IL-35-dependent.
Conclusion: To our knowledge, for the first time we demonstrated that synovial/peripheral B cells expressed IL-35R and were responsive to IL-35 stimulation. SF residing in RA synovium can be linked to B cell activation and maintenance in RA synovium through IL-35.
Databáze: MEDLINE