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Aberrant Expression of Regulatory Cytokine IL-35 and Pattern Recognition Receptor NOD2 in Patients with Allergic Asthma

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Abstract

We investigated the plasma concentration of the novel regulatory cytokine IL-35 and intracytosolic pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors in granulocytes and explored their potential implication in disease severity monitoring of allergic asthma. The expression of circulating IL-35 and other pro-inflammatory mediators in asthmatic patients or control subjects were evaluated using enzyme-linked immunosorbent assay (ELISA). The intracellular expressions of NOD1 and NOD2 in CCR3+ granulocytes were assessed using flow cytometry. Plasma concentrations of IL-35, IL-17A, basophil activation marker basogranulin, and eosinophilic airway inflammation biomarker periostin were significantly elevated in allergic asthmatic patients compared to non-atopic control subjects (all probability (p) <0.05). Both granulocyte markers exhibited significant and positive correlation with plasma IL-35 concentration in asthmatic patients (all p < 0.05). Significant positive correlation was also identified between plasma concentrations of IL-35 and periostin with disease severity score in asthmatic patients (both p < 0.05). The basophil activation allergenicity test was positive in allergic asthmatic patients but not in control subjects. Despite significantly elevated eosinophil count in allergic asthmatic patients, downregulation of NOD2 in CCR3+ granulocytes was observed in these patients (both p < 0.05). A negative correlation between plasma concentrations of tumor necrosis factor family member LIGHT and soluble herpesvirus entry mediator was observed in patients with elevated plasma concentration of IL-35 (p < 0.05). Aberrant expression of NOD2 in granulocytes may be contributed to the impaired innate immunity predisposing allergic asthma. IL-35 may serve as a potential surrogate biomarker for disease severity of allergic asthma.

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ACKNOWLEDGMENTS

This work was supported by the Research Grant Committee General Research Fund, Hong Kong (Project Ref. No. CUHK 476411, Principal investigator: CKW), National Natural Science Foundation of China (Grant no.: 81273248) and Direct Grant from The Chinese University of Hong Kong (project code: 2011.1.011).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong

    Chun Kwok Wong, Ida Miu Ting Chu, Jie Dong, Yvonne Yi On Lam & Christopher Wai Kei Lam

  2. Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, Hong Kong

    Chun Kwok Wong

  3. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China

    Chun Kwok Wong & Jie Dong

  4. Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong

    Ting Fan Leung

  5. State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau

    Christopher Wai Kei Lam

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Wong, C.K., Leung, T.F., Chu, I.M.T. et al. Aberrant Expression of Regulatory Cytokine IL-35 and Pattern Recognition Receptor NOD2 in Patients with Allergic Asthma. Inflammation 38, 348–360 (2015). https://doi.org/10.1007/s10753-014-0038-4

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