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The Role of TNF Family Molecules Light in Cellular Interaction Between Airway Smooth Muscle Cells and T Cells During Chronic Allergic Inflammation

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Abstract

Interaction between T cells and airway smooth muscle (ASM) cells has been identified as an important factor in the development of asthma. LIGHT (known as TNFSF14) -mediated signaling likely contributes to various inflammatory disorders and airway remodeling. The objective of this study was to investigate the roles of LIGHT-mediated pathways in the interaction between ASM cells and T cells during chronic allergic inflammation. Mice were sensitized and challenged by ovalbumin (OVA) to induce chronic airway allergic inflammation. The control group received PBS only. The histological features and LIGHT expressions in lungs were assessed in vivo. Furthermore, T cells and ASM cells derived from the model mice were co-cultured both in the presence and absence of anti-LIGHT Ab for 72 h. The effects of LIGHT blockade on expressions of downstream signaling molecules, proliferation, and apoptosis of ASM cells, differentiation of T cells, and inflammatory cytokines release were evaluated. We demonstrated that LIGHT blockade strikingly inhibited the mRNA and protein expressions of HVEM, c-JUN, and NFκB. Additionally, LIGHT blockade resulted in decreased proliferation and increased apoptosis of ASM cells. Moreover, depletion of LIGHT dramatically reduced the differentiation of CD4+ T cells into Th1, Th2, and Th17 cells, as well as inhibited inflammatory cytokines release including IL-13, TGF-β, and IFN-γ, which are associated with CD4+ T cell differentiation and ASM cell proliferation. LIGHT plays an important role in the interaction between T cells and ASM cells in chronic allergic asthma. Blockade of LIGHT markedly suppressed ASM hyperplasia and inflammatory responses, which might be modulated through HVEM-NFκB or c-JUN pathways. Therefore, targeting LIGHT is a promising therapeutic strategy for airway inflammation and remodeling in chronic allergic asthma.

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Acknowledgements

We thank Jinan University and Shenzhen-PKU-HKUST Medical Center for the use of resources and facilities.

Funding

The study was supported by the National Natural Science Foundation of China (Project Number: 81300012), the Science and Technology Planning Project of Guangdong Province, China (Project Number: 2016A020215025), the Medical Scientific Research Foundation of Guangdong Province, China (Project Number: A2016375), and the Shenzhen Science and Technology Innovation Committee Basic Science Research Grant (JCYJ20140416144209745, JCYJ20160427185306518).

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Authors and Affiliations

  1. Emergency Department, The Second Clinical College, Shenzhen People’s Hospital, Jinan University, NO.1017 Dongmen North Road, Shenzhen, 518020, China

    Fei Shi, Aijun Shan, Ying Yang & Binbin Li

  2. Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, The Hong Kong University of Science and Technology Medical Center, Shenzhen Peking University, Shenzhen, 518036, China

    Yi Xiong, Yarui Zhang & Manhui Li

  3. Pulmonary Department, The Second Clinical College, Shenzhen People’s Hospital, Jinan University, NO. 1017 Dongmen North Road, Shenzhen, 518020, China

    Chen Qiu

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  1. Fei Shi
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Correspondence to Fei Shi.

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Shi, F., Xiong, Y., Zhang, Y. et al. The Role of TNF Family Molecules Light in Cellular Interaction Between Airway Smooth Muscle Cells and T Cells During Chronic Allergic Inflammation. Inflammation 41, 1021–1031 (2018). https://doi.org/10.1007/s10753-018-0755-1

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