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Anti-inflammatory roles of interleukin-35 in the pathogenesis of Japanese cedar pollinosis.

KOUZAKI Hideaki 10402710 0000-0001-5460-4967 ARAI Yukihiro 60816627 0000-0002-9120-3035 NAKAMURA Keigo 50848380 0000-0003-2570-9529 MARUO Takuya 0000-0003-3092-6771 TOJIMA Ichiro 80567347 0000-0001-7687-9427 SHIMIZU Shino 50505592 0000-0002-0704-9048 YUTA Atsushi 0000-0002-4758-1346 SHIMIZU Takeshi 00206202 0000-0002-1344-7210 滋賀医科大学

2021.07.21

概要

Background:
Interleukin (IL)-35 has been recently identified as an anti-inflammatory cytokine in allergic inflammation. However, its biological role in the pathogenesis of allergic rhinitis has not been fully elucidated.
Objective:
The purpose of this study was to investigate the anti-inflammatory activity of IL-35 in the pathogenesis of allergic rhinitis in patients with Japanese cedar pollinosis (JCP).
Methods:
Peripheral blood mononuclear cells were collected from healthy controls and JCP patients during the off-season for pollen. Peripheral blood mononuclear cells were incubated with Cry j 1, a major allergen of Japanese cedar pollen and production of IL-5, IL-13, and IL-35 were measured by enzyme-linked immunosorbent assay. Th2 (CD4+ST2+) cells and group 2 innate lymphoid cells were isolated from peripheral blood mononuclear cells of JCP patients, and the inhibitory effects of IL-35 on cell differentiation, proliferation and mRNA expression of IL-5, IL-13, and GATA3 were examined. B cells were also isolated and the effects of IL-35 on total IgE production were examined.
Results:
Cry j 1-induced production of IL-5 and IL-13 was significantly increased in peripheral blood mononuclear cells from JCP patients, whereas Cry j 1-induced IL-35 production was significantly decreased compared with healthy controls. IL-35 significantly inhibited Th2 cell differentiation, group 2 innate lymphoid cell proliferation, and mRNA expression of IL-5, IL-13, and GATA3 in Th2 cells and group 2 innate lymphoid cells. IL-35 also inhibited IgE production from B cells.
Conclusion:
IL-35 is an important anti-inflammatory cytokine in JCP, and its biological roles include the downregulation of Th2 cells and group 2 innate lymphoid cells, and the inhibition of IgE production from B cells. These findings demonstrate that IL-35 may have the potential to exert anti-allergic effects for the treatment of allergic rhinitis.

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