Bortezomib restrains M2 polarization and reduces CXCL16-associated CXCR6+CD4 T cell chemotaxis in bleomycin-induced pulmonary fibrosis

• DOI: 10.1186/s10020-024-00836-5
• Publication Date: 2024-05-24T15:02:08Z
• Authors: Ting Zhou; Lan lin; Yawen Zhan; Ziyao Zhang; Ying Jiang; Mi Wu; Dan Xue; Limin Chen; Xiufang Weng; Zhenghui Huang
• Keywords: CD4-Positive T-Lymphocytes; Male; Antigens, Differentiation, T-Lymphocyte; Macrophage; Pulmonary Fibrosis; RM1-950; QD415-436; Biochemistry; Pulmonary fibrosis; Bortezomib; Bleomycin; Mice; 03 medical and health sciences; Antigens, CD; Animals; Lectins, C-Type; Receptors, CXCR6; 0303 health sciences; Macrophages; Chemotaxis; Chemokine CXCL16; CXCR6; CXCL16; Mice, Inbred C57BL; Disease Models, Animal; Therapeutics. Pharmacology; Research Article

Abstract Background The development of pulmonary fibrosis involves a cascade events, in which inflammation mediated by immune cells plays pivotal role. Chemotherapeutic drugs have been shown to dual effects on fibrosis, with bleomycin exacerbating and bortezomib alleviating tissue fibrotic processes. Understanding the intricate interplay between chemotherapeutic drugs, responses, is likely serve as foundation for crafting tailored therapeutic strategies. Methods A model bleomycin-induced was established, followed treatment bortezomib. Tissue samples were collected analysis cell subsets functional assessment flow cytometry vitro experiments. Additionally, multi-omics conducted further elucidate expression chemokines chemokine receptors, well characteristics populations. Results Here, we observed that CXCL16 CXCR6 elevated lung model. In context or TGF-β1 stimulation vitro, macrophages exhibited an M2-polarized phenotype secreted more than those control group. Moreover, revealed increased levels CD69 CD4 T during progression. administration alleviated accompanied reduced ratio decreased accumulation expressing CXCR6. Conclusions Our findings provide insights into key players involved offer preclinical evidence supporting repurposing strategy combination approaches reduce fibrosis.