The Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice
Yifang Chen,1,* Yang Li,1,* Han Guo,1,2,* Zhaoqi Zhang,1,2 Jiayu Zhang,1,2 Xue Dong,1 Yi Liu,3 Yuan Zhuang,3 Yong Zhao1,4 1Department of State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Savaid M...
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Dove Medical Press
2021
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oai:doaj.org-article:b27535b00e1f4220ae96785d89fb08672021-12-02T15:03:23ZThe Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice1178-7031https://doaj.org/article/b27535b00e1f4220ae96785d89fb08672021-09-01T00:00:00Zhttps://www.dovepress.com/the-effects-of-adoptively-transferred-il-23il-18-polarized-neutrophils-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Yifang Chen,1,* Yang Li,1,* Han Guo,1,2,* Zhaoqi Zhang,1,2 Jiayu Zhang,1,2 Xue Dong,1 Yi Liu,3 Yuan Zhuang,3 Yong Zhao1,4 1Department of State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of State Key Laboratory of Membrane Biology, Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Zhao; Yuan Zhuang Email zhaoy@ioz.ac.cn; zhuangyuan0215@126.comBackground: Neutrophils present great diverse phenotypes in various microenvironments and play different immune regulatory functions. Neutrophils generally classified into inflammatory phenotype N1 and anti-informatory phenotype N2. Our recent studies showed that IL-23 alone stimulated neutrophils to express IL-17A, IL-17F and IL-22 and displayed a gene transcriptional profile similar to Th17 cells. In the present study, we tried to identify potential cytokines to promote IL-23-induced neutrophil polarization.Methods: Mouse bone marrow-derived neutrophils and human peripheral blood neutrophils were treated with IL-23 (10 ng/mL) plus IL-18 (25 ng/mL) to induce Th17-like subset in vitro and detected by real-time PCR, flow cytometry, ELISA, immunofluorescence and RNA-seq assays. In vivo, collagen-induced arthritis (CIA) mouse model and EL4 tumor-bearing mouse model were used to characterize the potential roles of N(IL-23+IL-18) in inflammation and tumor.Results: Real-time PCR, ELISA and flow cytometry assays showed that IL-18 could significantly enhance IL-23-induced IL-17A, IL-17F and IL-22 expressions in mouse and human neutrophils in a synergistic way, although IL-18 alone failed to induce these cytokines expression. RNA-seq and molecular studies showed that the polarization of N(IL-23+IL-18) is mainly mediated by the JNK/p38-STAT3-BATF signaling pathway. Adoptive transfer of the induced N(IL-23+IL-18) neutrophils significantly accelerated the tumor growth in EL4 tumor-bearing mice and enhanced disease progression in the CIA mouse model. IL-17A-deficient N(IL-23+IL-18) neutrophils failed to enhance the CIA pathogenesis in this model, suggesting that IL-17A may be involved in the N(IL-23+IL-18) neutrophils-promoted arthritis in mice.Conclusion: The Th17-type subpopulation N(IL-23+IL-18) has pro-tumor and pro-inflammatory properties. Recognizing the different functional polarization of neutrophils would significantly help us to understand the distinctive protective/pathological roles of neutrophils in physiological and different pathological situations.Keywords: IL-23, IL-18, neutrophils, polarization, tumor, arthritisChen YLi YGuo HZhang ZZhang JDong XLiu YZhuang YZhao YDove Medical Pressarticleil-23il-18neutrophilspolarizationtumorarthritisPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4669-4686 (2021) |
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DOAJ |
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EN |
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il-23 il-18 neutrophils polarization tumor arthritis Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
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il-23 il-18 neutrophils polarization tumor arthritis Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Chen Y Li Y Guo H Zhang Z Zhang J Dong X Liu Y Zhuang Y Zhao Y The Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice |
| description |
Yifang Chen,1,* Yang Li,1,* Han Guo,1,2,* Zhaoqi Zhang,1,2 Jiayu Zhang,1,2 Xue Dong,1 Yi Liu,3 Yuan Zhuang,3 Yong Zhao1,4 1Department of State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Savaid Medical School, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 3Department of Blood Transfusion, First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of State Key Laboratory of Membrane Biology, Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Zhao; Yuan Zhuang Email zhaoy@ioz.ac.cn; zhuangyuan0215@126.comBackground: Neutrophils present great diverse phenotypes in various microenvironments and play different immune regulatory functions. Neutrophils generally classified into inflammatory phenotype N1 and anti-informatory phenotype N2. Our recent studies showed that IL-23 alone stimulated neutrophils to express IL-17A, IL-17F and IL-22 and displayed a gene transcriptional profile similar to Th17 cells. In the present study, we tried to identify potential cytokines to promote IL-23-induced neutrophil polarization.Methods: Mouse bone marrow-derived neutrophils and human peripheral blood neutrophils were treated with IL-23 (10 ng/mL) plus IL-18 (25 ng/mL) to induce Th17-like subset in vitro and detected by real-time PCR, flow cytometry, ELISA, immunofluorescence and RNA-seq assays. In vivo, collagen-induced arthritis (CIA) mouse model and EL4 tumor-bearing mouse model were used to characterize the potential roles of N(IL-23+IL-18) in inflammation and tumor.Results: Real-time PCR, ELISA and flow cytometry assays showed that IL-18 could significantly enhance IL-23-induced IL-17A, IL-17F and IL-22 expressions in mouse and human neutrophils in a synergistic way, although IL-18 alone failed to induce these cytokines expression. RNA-seq and molecular studies showed that the polarization of N(IL-23+IL-18) is mainly mediated by the JNK/p38-STAT3-BATF signaling pathway. Adoptive transfer of the induced N(IL-23+IL-18) neutrophils significantly accelerated the tumor growth in EL4 tumor-bearing mice and enhanced disease progression in the CIA mouse model. IL-17A-deficient N(IL-23+IL-18) neutrophils failed to enhance the CIA pathogenesis in this model, suggesting that IL-17A may be involved in the N(IL-23+IL-18) neutrophils-promoted arthritis in mice.Conclusion: The Th17-type subpopulation N(IL-23+IL-18) has pro-tumor and pro-inflammatory properties. Recognizing the different functional polarization of neutrophils would significantly help us to understand the distinctive protective/pathological roles of neutrophils in physiological and different pathological situations.Keywords: IL-23, IL-18, neutrophils, polarization, tumor, arthritis |
| format |
article |
| author |
Chen Y Li Y Guo H Zhang Z Zhang J Dong X Liu Y Zhuang Y Zhao Y |
| author_facet |
Chen Y Li Y Guo H Zhang Z Zhang J Dong X Liu Y Zhuang Y Zhao Y |
| author_sort |
Chen Y |
| title |
The Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice |
| title_short |
The Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice |
| title_full |
The Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice |
| title_fullStr |
The Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice |
| title_full_unstemmed |
The Effects of Adoptively Transferred IL-23/IL-18-Polarized Neutrophils on Tumor and Collagen-Induced Arthritis in Mice |
| title_sort |
effects of adoptively transferred il-23/il-18-polarized neutrophils on tumor and collagen-induced arthritis in mice |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/b27535b00e1f4220ae96785d89fb0867 |
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