Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis.

Souichiro Nakano, Shinji Morimoto, Satoshi Suzuki, Hiroshi Tsushima, Kenjiro Yamanaka, Iwao Sekigawa, Yoshinari Takasaki

Index: Rheumatology (Oxford.) 54 , 1498-506, (2015)

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Abstract

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.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.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.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.© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.