Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis.
OBJECTIVE
IL-35 is the most recently identified member of the IL-12 family. It consists of EBV-induced gene 3 (EBI3) and IL-12α chain p35. We investigated whether IL-35 enhances the in vitro immunosuppressive function of peripheral blood isolated from patients with RA.


METHODS
Peripheral blood was harvested from 17 active and 10 inactive RA patients and IL-35 concentrations were quantified using an ELISA. An expression vector containing IL-35 with a FLAG tag at the carboxyl-terminus was constructed by covalently linking EBI3 and IL-12α (p35). The function of IL-35 was then evaluated in a suppression assay using T cells isolated from human RA patients with CD2, CD3 and CD28 antibodies.


RESULTS
Serum IL-35 levels and the number of Treg were decreased significantly in patients with active RA. There was a significant correlation between serum IL-35 and the 28-joint DAS with ESR (DAS28-ESR) in patients with active RA. IL-35 treatment enhanced the regulatory function, suppressing the levels of inflammatory cytokines such as IL-17 and IFN-γ and the cellular growth of effector T cells stimulated by conjugation with CD2, CD3 and CD28.


CONCLUSIONS
These data revealed that IL-35 might suppress T cell activation during the peripheral immune responses of RA. Therefore our data suggest that IL-35 might have multiple therapeutic targets.
Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, Tokyo, soubey@juntendo.ac.jp.
Souichiro
S
Nakano
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba and.
Shinji
S
Morimoto
Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, Tokyo.
Satoshi
S
Suzuki
Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, Tokyo.
Hiroshi
H
Tsushima
Department of Rheumatology and Internal Medicine, Sasaki Foundation, Tokyo, Japan.
Kenjiro
K
Yamanaka
Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba and.
Iwao
I
Sekigawa
Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, Tokyo.
Yoshinari
Y
Takasaki
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015551:Autoimmunity / Q000502:physiology*; D018801:CD2 Antigens / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D016022:Case-Control Studies; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000473:pathology / Q000502:physiology*
D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D007378:Interleukins; C532417:interleukin-35, human; D016753:Interleukin-10
DAS28-CRP; IFN-γ; IL-17; IL-35; regulatory T cells; rheumatoid arthritis; suppressive function