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AB0064 Role of il-35 in the regulation of immune response in patients with rheumatoid arthritis
  1. I. Adamova1,
  2. M. Mravcova1,
  3. M. Vlcek1,
  4. A. Penesova1,
  5. K. Krskova1,
  6. Z. Radikova1,
  7. A. Havranova1,
  8. R. Imrich1,2
  1. 1Biomedical Research Center, Slovak Academy of Sciences, Bratislava
  2. 2National Institute of Rheumatic Diseases, Piestany, Slovakia


Background Interleukin 35 (IL-35) is a recently identified member of the IL-12 family of cytokines and represents a novel target for therapies of autoimmune, inflammatory, and infectious diseases, including rheumatoid arthritis (RA).Choi et al. 2015

IL-35 is a heterodimer consisting of EBV-induced gene 3 (EBI3) and IL-12α chain p35 (Nakano et al. 2015). In contrast to other IL-12 cytokine family members, IL-35 appears to have anti-inflammatory and immunosuppressive properties mediated by induction of regulatory T and B cells; (Choi et al. 2015. Huang et al. 2017). In particular, IL-35 may play an important role in suppressing the inflammatory response by expanding regulatory T cells and in dampening the differentiation of Th17 cells (Niedbala et al. 2007).

Objectives This study was designed to analyse effects of IL-35 on stimulated peripheral blood mononuclear cells (PBMC) and their subpopulations in RA patients and healthy controls.

Methods PBMCs of 10 RA patients and 10 controls as well as CD14 +and CD4+cells isolated from PBMCs using magnetic separation were cultured for 24 hours, and subjected to three conditions: no stimulation, stimulation with LPS (PBMC and CD14+) or stimulation with anti-CD3/anti-CD28 antibodies (PBMC and CD4+), and stimulation with added IL-35 (100 ng/ml). A panel of nine cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12 (p70), IL-17a, IFN-γ, MIP-1β and TNF) was analysed in the cell culture supernatants.

Results RA patients had higher serum levels of IL-35 compared to healthy controls. A decreased secretion of IL-8 and increased secretion of TNF in the presence of IL-35 was observed in vitro in stimulated PBMCs of RA patients. In the control group, we observed an increased secretion of IL-6 by PBMCs and decreased secretion of IL-10 by T lymphocytes as a result of IL-35 addition to stimulated cells.

Conclusions In this study, we found elevated serum levels of IL-35 in RA patients suggesting a possible involvement of IL-35 in the pathogenesis of RA. However, in vitro, the effect of IL-35 on stimulated immune cells was partially anti-inflammatory and partially pro-inflammatory, suggesting that the effect of IL-35 is pleiotropic and depends on the type and the state of the affected immune cell.

References [1] Huang A, Cheng L, He M, et al. Interleukin-35 on B cell and T cell induction and regulation. J. Inflamm. (United Kingdom)2017;14.

[2] Choi J, Leung PSC, Bowlus C, Gershwin ME. IL-35 and Autoimmunity: a Comprehensive Perspective. Clin Rev Allergy Immunol2015;49:327–332. doi:10.1007/s12016-015-8468-9

[3] Nakano S, Morimoto S, Suzuki S, et al. Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis. Rheumatology (Oxford)2015;54:1498–1506. doi:10.1093/rheumatology/keu528

[4] Niedbala W, Wei XQ, Cai B, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol2007;37:3021–3029. doi:10.1002/eji.200737810

Acknowledgements Grant support: APVV-15–0228 and VEGA 2/0161/16

Disclosure of Interest None declared

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