Bortezomib restrains M2 polarization and reduces CXCL16-associated CXCR6+CD4 T cell chemotaxis in bleomycin-induced pulmonary fibrosis
Abstract Background The development of pulmonary fibrosis entails a cascade of events, where immune cell-mediated inflammation plays a central role. Chemotherapeutic drugs have been observed to exert dual impacts on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processing. Understanding of the complex interactions between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies. Methods A bleomycin-induced pulmonary fibrosis model was established, followed by bortezomib treatment. Tissue samples were collected for immune cell subset analysis and functional evaluation through flow cytometry and in vitro cell experiments. Additionally, multi-omics analysis was conducted to further elucidate the expression of chemokines and chemokine receptors and the characteristics of cell populations. Result Here, we noticed that CXCL16 and CXCR6 were elevated in the lung tissue of pulmonary fibrosis model. In the context of pulmonary fibrosis or in vitro TGF-β1 stimulation, macrophages exhibited M2-polarized phenotype and secreted more CXCL16 compared with control group. In addition, flow cytometry revealed that pulmonary CD4 T cells expressed higher CD69 and CXCR6 levels in fibrosis progress. Upon administration of bortezomib, bleomycin-induced pulmonary fibrosis was alleviated accompanied by decreased M2-polarized macrophages and reduced accumulation of CXCR6-expressing CD4 T cells. Conclusions Our findings provide insights into the key immune players in bleomycin-induced pulmonary fibrosis and offer the preclinical evidence supporting the repurposing strategy and combination approach to reduced lung fibrosis..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 07. Feb. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhou, Ting [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.21203/rs.3.rs-3907780/v1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XRA042439361 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | XRA042439361 | ||
| 003 | DE-627 | ||
| 005 | 20240208131522.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240208s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.21203/rs.3.rs-3907780/v1 |2 doi | |
| 035 | |a (DE-627)XRA042439361 | ||
| 035 | |a (ResearchSquare)10.21203/rs.3.rs-3907780/v1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhou, Ting |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Bortezomib restrains M2 polarization and reduces CXCL16-associated CXCR6+CD4 T cell chemotaxis in bleomycin-induced pulmonary fibrosis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Background The development of pulmonary fibrosis entails a cascade of events, where immune cell-mediated inflammation plays a central role. Chemotherapeutic drugs have been observed to exert dual impacts on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processing. Understanding of the complex interactions between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies. Methods A bleomycin-induced pulmonary fibrosis model was established, followed by bortezomib treatment. Tissue samples were collected for immune cell subset analysis and functional evaluation through flow cytometry and in vitro cell experiments. Additionally, multi-omics analysis was conducted to further elucidate the expression of chemokines and chemokine receptors and the characteristics of cell populations. Result Here, we noticed that CXCL16 and CXCR6 were elevated in the lung tissue of pulmonary fibrosis model. In the context of pulmonary fibrosis or in vitro TGF-β1 stimulation, macrophages exhibited M2-polarized phenotype and secreted more CXCL16 compared with control group. In addition, flow cytometry revealed that pulmonary CD4 T cells expressed higher CD69 and CXCR6 levels in fibrosis progress. Upon administration of bortezomib, bleomycin-induced pulmonary fibrosis was alleviated accompanied by decreased M2-polarized macrophages and reduced accumulation of CXCR6-expressing CD4 T cells. Conclusions Our findings provide insights into the key immune players in bleomycin-induced pulmonary fibrosis and offer the preclinical evidence supporting the repurposing strategy and combination approach to reduced lung fibrosis. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Lin, Lan |4 aut | |
| 700 | 1 | |a Zhan, Yawen |4 aut | |
| 700 | 1 | |a Zhang, Ziyao |4 aut | |
| 700 | 1 | |a Jiang, Ying |4 aut | |
| 700 | 1 | |a Wu, Mi |4 aut | |
| 700 | 1 | |a Xue, Dan |4 aut | |
| 700 | 1 | |a Chen, Limin |4 aut | |
| 700 | 1 | |a Weng, Xiufang |4 aut | |
| 700 | 1 | |a Huang, Zhenghui |0 (orcid)0009-0004-2883-5197 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ResearchSquare.com |g (2024) vom: 07. Feb. |
| 773 | 1 | 8 | |g year:2024 |g day:07 |g month:02 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.21203/rs.3.rs-3907780/v1 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XRA | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 07 |c 02 | ||