Inhibited interleukin 35 expression and interleukin 35-induced regulatory T cells promote type II innate lymphoid cell response in allergic rhinitis.

Wenlong Liu, Qingxiang Zeng, Yanhui Wen, Yiquan Tang, Shengbao Yan, Yan Li, Lifeng Zhou, Renzhong Luo

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 2021 Feb

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Interleukin (IL)-35 and IL-35-producing regulatory T cells (iTr35) have been reported to inhibit TH2 response in allergic rhinitis (AR). However, its effects on type II innate lymphoid cells (ILC2) are not well characterized. To investigate the effect of IL-35 on ILC2 in AR. A total of 25 patients with AR and 20 controls were recruited. The expression and regulation of IL-35 receptor in ILC2 were analyzed by real-time polymerase chain reaction. The effect of IL-35 on ILC2 differentiation and cytokine production was analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, iTr35 were cocultured with ILC2 to explore the effect of iTr35 on ILC2. The AR mice models were also established to confirm the role of IL-35 in vivo. The patients with AR had decreased IL-35 expression and iTr35 proportion and increased ILC2 and type II cytokines compared with the controls. Notably, IL-35 inhibited ILC2 differentiation and type II cytokine production by regulating IL-12Rβ2 and gp130. IL-35 promoted the inducible costimulatory molecule expression by iTr35 and the inducible costimulatory molecule ligand expression by ILC2. IL-35-treated mice with AR presented decreased frequency and function of nasal ILC2. IL-35 inhibited ILC2 responses directly or through mutual contact between iTr35 and ILC2 in AR, suggesting that IL-35 may be used as a potential treatment target in AR. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Wenlong Liu, Qingxiang Zeng, Yanhui Wen, Yiquan Tang, Shengbao Yan, Yan Li, Lifeng Zhou, Renzhong Luo. Inhibited interleukin 35 expression and interleukin 35-induced regulatory T cells promote type II innate lymphoid cell response in allergic rhinitis. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2021 Feb;126(2):152-161.e1