Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling. (September 2021)

• Record Type: Journal Article
• Authors: Wang, Yaping; Liu, Bo; Niu, Chao; Zou, Wenjing; Yang, Lili; Wang, Ting; Tian, Daiyin; Luo, Zhengxiu; Dai, Jihong; Li, Qubei; Liu, Enmei; Gong, Caihui; Fu, Zhou; Ding, Fengxia
• Is Part Of: Molecular immunology. Volume 137(2021)
• Page Start: 238
• Page End: 246
• Publication Date: 2021-09
• Subjects: GITRL glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand -- GITR glucocorticoid-induced tumor necrosis factor receptor-related receptor -- NF-κB nuclear factor-κB -- MAPKs mitogen-activated protein kinases -- Erk extracellular signal-regulated kinase -- JNK jun N-terminal kinase -- HDM house dust mite -- AHR airway hyperresponsiveness -- APCs antigen-presenting cells -- BALF bronchoalveolar lavage fluid -- AAV adeno-associated virus -- GFP green fluorescent protein -- TNFSF tumor necrosis factor superfamily -- MFI mean fluorescence intensity -- BSA bovine serum albumin -- IOD integral optical density -- PBS phosphate buffer -- TRAFs TNFR associated factors; GITRL/GITR -- Asthma -- MAPKs -- NF-κB -- Adeno-associated virus; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.07.005
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: GITRL and GITR are highly expressed in HDM-induced asthma. GITRL/GITR-MAPK/NF-κB signaling pathway is activated in HDM-induced asthma. Knockdown of GITRL reduces allergic airway inflammation and airway hyperresponsiveness induced by HDM. GITRL knockdown inhibits the activation of GITRL/GITR-MAPKs/NF-κB signaling pathway. Abstract: GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.