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- Title
Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis.
- Authors
Souichiro Nakano; Shinji Morimoto; Satoshi Suzuki; Hiroshi Tsushima; Kenjiro Yamanaka; Iwao Sekigawa; Yoshinari Takasaki
- Abstract
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 immunosup-pressive 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. Conclusion. 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.
- Subjects
JAPAN; T cells; ACADEMIC medical centers; BLOOD testing; STATISTICAL correlation; CYTOKINES; ENZYME-linked immunosorbent assay; IMMUNOBLOTTING; IMMUNOGLOBULINS; IMMUNOSUPPRESSION; INTERFERONS; INTERLEUKINS; POLYMERASE chain reaction; RESEARCH funding; RHEUMATOID arthritis; DESCRIPTIVE statistics; IN vitro studies; MANN Whitney U Test; PHYSIOLOGY
- Publication
Rheumatology, 2015, Vol 54, Issue 8, p1498
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/keu528