PMID- 29247146
OWN - NLM
STAT- MEDLINE
DCOM- 20191211
LR  - 20191217
IS  - 1499-2752 (Electronic)
IS  - 0315-162X (Linking)
VI  - 45
IP  - 4
DP  - 2018 Apr
TI  - Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with 
      Osteoarthritis and Rheumatoid Arthritis.
PG  - 563-573
LID - 10.3899/jrheum.161363 [doi]
AB  - 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-alpha (TNF-alpha) 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-27Ralpha, but not IL-12Rbeta2, 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-27Ralpha 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-alpha-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.
FAU - Kam, Ngar-Woon
AU  - Kam NW
AD  - 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.
AD  - 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.
FAU - Liu, Dehua
AU  - Liu D
AD  - 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.
AD  - 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.
FAU - Cai, Zhe
AU  - Cai Z
AD  - 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.
AD  - 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.
FAU - Mak, Wah-Yan
AU  - Mak WY
AD  - 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.
AD  - 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.
FAU - Wong, Chun-Kwok
AU  - Wong CK
AD  - 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.
AD  - 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.
FAU - Chiu, Kwok-Hing
AU  - Chiu KH
AD  - 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.
AD  - 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.
FAU - Wong, Kam-Yiu
AU  - Wong KY
AD  - 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.
AD  - 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.
FAU - Tsang, Wai-Leuk
AU  - Tsang WL
AD  - 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.
AD  - 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.
FAU - Tam, Lai-Shan
AU  - Tam LS
AD  - 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.
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171215
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Antibodies)
RN  - 0 (IL4 protein, human)
RN  - 0 (Interleukins)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (interleukin-35, human)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Aged
MH  - Antibodies
MH  - Arthritis, Rheumatoid/*immunology
MH  - B-Lymphocytes/*metabolism
MH  - Coculture Techniques
MH  - Female
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - Interleukin-4
MH  - Interleukins/immunology/*metabolism
MH  - Lymphocyte Activation
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis/*immunology
MH  - Receptors, Interleukin/metabolism
MH  - Statistics, Nonparametric
MH  - Synovial Membrane/pathology
MH  - Synoviocytes/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - B CELLS
OT  - INTERLEUKIN 35
OT  - RHEUMATOID ARTHRITIS
OT  - SYNOVIAL FIBROBLAST
OT  - SYNOVIUM
EDAT- 2017/12/17 06:00
MHDA- 2019/12/18 06:00
CRDT- 2017/12/17 06:00
PHST- 2017/09/29 00:00 [accepted]
PHST- 2017/12/17 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2017/12/17 06:00 [entrez]
AID - jrheum.161363 [pii]
AID - 10.3899/jrheum.161363 [doi]
PST - ppublish
SO  - J Rheumatol. 2018 Apr;45(4):563-573. doi: 10.3899/jrheum.161363. Epub 2017 Dec 
      15.