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Critical role of IL-6 in dendritic cell-induced allergic inflammation of asthma

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Abstract

Interleukin (IL)-6 plays important roles in autoimmunity and inflammation and is essential for T helper (Th) 2 and Th17 differentiation. However, whether it is involved in the development and function of dendritic cells (DCs) during allergen-induced airway inflammation and airway hyper-reactivity (AHR) remains undefined. In this study, Dermatophagoides pteronyssinus (Der p)-induced airway inflammation and AHR were studied in IL-6 knockout (KO) mice. Der p-loaded bone marrow-derived DCs (BMDCs) from IL-6 KO mice were used to assaying their ability to induce airway inflammation in naïve wild-type mice. Our results showed that IL-6 KO mice showed reduced AHR, significant decreases in inflammatory cell recruitment and Th2 and Th17 cytokine production in the airways, and lowered Der p-specific immunoglobulin G1 after Der p exposure. Further exploration of BMDCs from IL-6 KO mice revealed decreased activity of phagocytosis and reduced expression of MHC class II and CD86 after Der p stimulation. Adoptive transfer of Der p-loaded BMDCs from IL-6 KO mice also showed a functional defect in their inability to induce Th2 and Th17 immune responses and trigger airway inflammation and AHR in recipient mice. Finally, in allergic asthmatics, DCs that differentiated from monocytes treated with anti-IL-6 receptor antibody (tocilizumab) had poor capacity for eliciting Th2 polarization as compared to DCs generated from monocytes without antibody treatment. In conclusion, IL-6 signaling in DCs is essential for their uptake of allergens, maturation, and initiation of Th2/Th17-mediated airway inflammation and AHR in asthma, thus providing a new potential target for treating allergic asthma.

Key messages

  • IL-6 signaling is important for DCs to take up allergens and to initiate Th2/Th17-mediated airway inflammation.

  • DCs from allergic asthmatics treated with anti-IL-6 receptor antibody had poor capacity for eliciting Th2 polarization.

  • Anti-IL-6 treatment may provide a new potential target for treating allergic asthma.

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Acknowledgments

This work was supported by the Ministry of Science and Technology (MOST), Taiwan, under grant number NSC 96-2314-B-006-027-MY3.

Author contributions

YLL designed the research, performed the studies, analyzed the data, interpreted the results, and wrote the manuscript. SHC designed the research and revised the manuscript. JYW designed the research, interpreted the results, and revised the manuscript.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Yen-Lin Lin & Jiu-Yao Wang

  2. Institute of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Shun-Hua Chen

  3. Allergy and Clinical Immunology Research (ACIR) Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Jiu-Yao Wang

  4. China Medical University Children Hospital, Taichung, Taiwan

    Jiu-Yao Wang

  5. Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan

    Jiu-Yao Wang

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  1. Yen-Lin Lin
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Correspondence to Jiu-Yao Wang.

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Lin, YL., Chen, SH. & Wang, JY. Critical role of IL-6 in dendritic cell-induced allergic inflammation of asthma. J Mol Med 94, 51–59 (2016). https://doi.org/10.1007/s00109-015-1325-8

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  • DOI: https://doi.org/10.1007/s00109-015-1325-8

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