Triggering receptor expressed on myeloid cells-1 aggravates obliterative bronchiolitis via enhancing the proinflammatory phenotype of macrophages.

Autor: Wan J; Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Yang F; Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Tong S; Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., Zhou T; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: Med.science@139.com., Wang S; Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: sihua_wang@126.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 1), pp. 113274. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1016/j.intimp.2024.113274
Abstrakt: Background: Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) plays an important role in innate immune system. However, whether and how TREM-1 contributes to obliterative bronchiolitis (OB) progression remains unclear.
Methods: A murine orthotopic tracheal transplantation model was constructed to mimic the pathogenesis of OB. qPCR and immunoblotting were used to measure TREM-1 expression. RNA sequencing was used to investigate the impact of TREM-1 on proinflammatory phenotype of macrophages. Trem-1 knockout mice and Nlrp3 knockout mice were generated to investigate the role of the TREM-1/NLRP3 pathway in the proinflammatory phenotype of macrophages. The infiltration of immune cells within the grafts was quantified using immunofluorescence staining. Flow cytometry was used to detect the proportion of different immune cells in mice spleen and the expression levels of iNOS and co-stimulatory molecules in macrophages.
Results: The expression of TREM-1 was upregulated in the mouse OB model. Genetic ablation or pharmacological inhibition of TREM-1 ameliorated OB, whereas the stimulation of TREM-1 using anti-TREM-1 agonistic antibody exacerbated OB. Moreover, Trem-1 ablation reduced the infiltration of iNOS + macrophages and limited the T cell responses. In vitro studies revealed that Trem-1 deletion impaired the proinflammatory function and antigen presentation ability of macrophages. Additionally, Trem-1 knockout inhibited the activation of NLRP3 signaling pathway. NLRP3 overexpression restored the proinflammatory phenotype of Trem-1 knockout macrophages.
Conclusions: These findings indicated that TREM-1 could promote the proinflammatory phenotype of macrophages through NLRP3 inflammasome activation, thereby exacerbating OB progression. These findings indicated that TREM-1 may serve as a therapeutic target for OB treatment.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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