2. Academic Validation
  3. Anti-DLL4 ameliorates toluene diisocyanate-induced experimental asthma by inhibiting Th17 response

Anti-DLL4 ameliorates toluene diisocyanate-induced experimental asthma by inhibiting Th17 response

  • Int Immunopharmacol. 2021 May:94:107444. doi: 10.1016/j.intimp.2021.107444.
Yao Deng 1,  Shuyu Chen 2,  Shijie Song 1,  Yin Huang 1,  Rongchang Chen 3,  Ailin Tao 4
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510260, China.
  • 2 The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510260, China; Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen 518020, China; The First Affiliated Hospital, Jinan University, Guangzhou, China.
  • 3 Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen 518020, China.
  • 4 The Second Affiliated Hospital, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510260, China. Electronic address: taoailin@gzhmu.edu.cn.
PMID: 33578263 DOI: 10.1016/j.intimp.2021.107444
Abstract

Toluene diisocyanate (TDI) exhibits an ability to induce steroid insensitive asthma with the involvement of Th17 cells. And emerging evidence has indicated that DLL4 signaling promotes Th17 differentiation through directly upregulating Rorc and IL-17 transcription. Thus, we sought to evaluate the effects of DLL4 blocking antibody on TDI-induced asthma model. Female BALB/c mice were sensitized and challenged with TDI to generate an asthma model. TDI-exposed mice were intraperitoneally injected with anti-DLL4 antibody and then analyzed for various parameters of the airway inflammatory responses. Increased expression of DLL4 in spleen and lung was detected in TDI-exposed mice. Furthermore, anti-DLL4 treatment alleviated TDI-induced airway hyperreactivity (AHR), airway inflammation, airway epithelial injury and airway smooth muscle (ASM) thickening. In the meantime, neutralizing DLL4 also blunted Th17 response via downregulation of ROR-γt expression, while had no effect on Th2 cells and regulatory T (Treg) cells. Overall, anti-DLL4 ameliorated TDI-induced experimental asthma by inhibiting Th17 response, implying the feasibility of targeting DLL4 for therapy of Th17-predominant severe asthma.

Keywords

Asthma; Delta-like 4; Th17 cells; Toluene diisocyanate.

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