IL-35 inhibits human osteoclastogenesis from monocytes induced by receptor-activator of NF-κB ligand

Toru Yago; Yuki Nanke; Manabu Kawamoto; Tsuyoshi Kobashigawa; Hisashi Yamanaka; Shigeru Kotake

doi:10.5114/ceji.2018.77384

eISSN: 1644-4124
ISSN: 1426-3912

Central European Journal of Immunology

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2/2018
vol. 43

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abstract:

Clinical immunology

IL-35 inhibits human osteoclastogenesis from monocytes induced by receptor-activator of NF-κB ligand

Toru Yago

,

Yuki Nanke

,

Manabu Kawamoto

,

Tsuyoshi Kobashigawa

,

Hisashi Yamanaka

,

Shigeru Kotake

(Centr Eur J Immunol 2018; 43 (2): 148-154)

DOI: https://doi.org/10.5114/ceji.2018.77384

Online publish date: 2018/06/30

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IL-35 is known as a regulatory cytokine produced by regulatory T cells. It has also been reported that IL-35 suppresses the proliferation of Th17 cells, which is involved in the pathogenesis of many autoimmune diseases. However, in rheumatoid arthritis patients, the role of IL-35 is controversial, and the role of IL-35 in bone metabolism has not been clarified. We investigated the effect of IL-35 on human osteoclast differentiation and activation. We first evaluated the effect of rhIL-35 on human osteoclastogenesis from monocytes cultured alone, induced by soluble-RANKL. We also examined the role of IL-35 on the bone-resorption function of mature osteoclasts. Furthermore, we analysed the molecular mechanism of IL-35 function in monocytes or pre-osteoclasts using RT-PCR. rhIL-35 significantly inhibited human osteoclastogenesis in a dose-dependent manner. In addition, rhIL-35 also significantly decreased the area of pit formation by mature osteoclasts. rhIL-35 significantly decreased mRNA expression of RANK in monocytes and RANK and FOS in pre-osteoclasts. Our current findings suggest that IL-35 inhibits osteoclastogenesis and osteoclast activation by inhibiting both RANK and FOS. IL-35 also has an inhibitory effect on osteoclastic-bone resorption, suggesting that IL-35 may have a therapeutic potential for RA.

keywords:

IL-35 inhibits human osteoclastogenesis from monocytes induced by receptor-activator of NF-κB ligand

Toru Yago , Yuki Nanke , Manabu Kawamoto , Tsuyoshi Kobashigawa , Hisashi Yamanaka , Shigeru Kotake

osteoclasts, monocytes, RANKL, Interleukin-35, osteoclastogenesis

Toru Yago

,

Yuki Nanke

,

Manabu Kawamoto

,

Tsuyoshi Kobashigawa

,

Hisashi Yamanaka

,

Shigeru Kotake