microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis
The microRNAs miR-144/451 are highly conserved miRNA that is strongly induced during erythropoiesis. Despite the biological functions of miR-144/451 have been extensively studied in erythropoiesis and tumorigenesis, few studies have been conducted in immune responses. In this study, we showed that m...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.928593/full |
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| author | Zhijie Lin Zhijie Lin Xiaoyan Xie Min Gu Qian Chen Guotao Lu Xiaoqin Jia Weiming Xiao Jun Zhang Duonan Yu Weijuan Gong Weijuan Gong Weijuan Gong Weijuan Gong Weijuan Gong |
| author_facet | Zhijie Lin Zhijie Lin Xiaoyan Xie Min Gu Qian Chen Guotao Lu Xiaoqin Jia Weiming Xiao Jun Zhang Duonan Yu Weijuan Gong Weijuan Gong Weijuan Gong Weijuan Gong Weijuan Gong |
| author_sort | Zhijie Lin |
| collection | DOAJ |
| description | The microRNAs miR-144/451 are highly conserved miRNA that is strongly induced during erythropoiesis. Despite the biological functions of miR-144/451 have been extensively studied in erythropoiesis and tumorigenesis, few studies have been conducted in immune responses. In this study, we showed that miR-144/451-/- DCs exhibit increased activation. Mechanistically, the miR-144 directly targets the 3`-UTR of IRF5 and represses the expression of IRF5 in DCs. Ectopic expression of miR-144/451 by lentiviruses downregulates the levels of IRF5 and suppresses DCs function. In addition, knockdown of IRF5 by shRNA significantly inhibits activities of the miR-144/451-/- DCs. Expression of miR144/451 was decreased in DCs from both patients with IBD and mice with DSS-colitis compared with controls. Human PBMC derived DCs were downregulated expression of miR144/451 after LPS stimulation. In the DSS-induced colitis mice model, we showed that ablation of the miR-144/451 gene causes severe colitis, and their DCs from both periphery and MLN expressed higher co-stimulatory molecules and pro-inflammatory cytokines than wild-type mice. In addition, DCs isolated from miR-144/451-/- mice transfusion exacerbates mice colitis. In the bone marrow transplanted chimeric mice model, we show that miR-144/451-/- bone marrow transplantation deteriorated DSS-induced colitis. At last, we treat the mice with miR-144/451 delivered by chitosan nanoparticles revealing protective effects in DSS-induced colitis mice. Thus, our results reveal a novel miR144/451-IRF5 pathway in DCs that protects experimental colitis. The manipulation of miR-144/451 expression and DCs activation in IBD patients may be a novel therapeutic approach for the treatment of inflammatory diseases. |
| first_indexed | 2024-12-10T08:44:24Z |
| format | Article |
| id | doaj.art-bca4d42b65214d37bd03dc54b4a9378c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T08:44:24Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bca4d42b65214d37bd03dc54b4a9378c2022-12-22T01:55:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.928593928593microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitisZhijie Lin0Zhijie Lin1Xiaoyan Xie2Min Gu3Qian Chen4Guotao Lu5Xiaoqin Jia6Weiming Xiao7Jun Zhang8Duonan Yu9Weijuan Gong10Weijuan Gong11Weijuan Gong12Weijuan Gong13Weijuan Gong14Department of Immunology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University, Yangzhou, ChinaDepartment of Immunology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, ChinaDepartment of Immunology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, ChinaDepartment of Immunology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaDepartment of Blood Transfusion, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University, Yangzhou, ChinaDepartment of Immunology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University, Yangzhou, ChinaDepartment of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, ChinaThe microRNAs miR-144/451 are highly conserved miRNA that is strongly induced during erythropoiesis. Despite the biological functions of miR-144/451 have been extensively studied in erythropoiesis and tumorigenesis, few studies have been conducted in immune responses. In this study, we showed that miR-144/451-/- DCs exhibit increased activation. Mechanistically, the miR-144 directly targets the 3`-UTR of IRF5 and represses the expression of IRF5 in DCs. Ectopic expression of miR-144/451 by lentiviruses downregulates the levels of IRF5 and suppresses DCs function. In addition, knockdown of IRF5 by shRNA significantly inhibits activities of the miR-144/451-/- DCs. Expression of miR144/451 was decreased in DCs from both patients with IBD and mice with DSS-colitis compared with controls. Human PBMC derived DCs were downregulated expression of miR144/451 after LPS stimulation. In the DSS-induced colitis mice model, we showed that ablation of the miR-144/451 gene causes severe colitis, and their DCs from both periphery and MLN expressed higher co-stimulatory molecules and pro-inflammatory cytokines than wild-type mice. In addition, DCs isolated from miR-144/451-/- mice transfusion exacerbates mice colitis. In the bone marrow transplanted chimeric mice model, we show that miR-144/451-/- bone marrow transplantation deteriorated DSS-induced colitis. At last, we treat the mice with miR-144/451 delivered by chitosan nanoparticles revealing protective effects in DSS-induced colitis mice. Thus, our results reveal a novel miR144/451-IRF5 pathway in DCs that protects experimental colitis. The manipulation of miR-144/451 expression and DCs activation in IBD patients may be a novel therapeutic approach for the treatment of inflammatory diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2022.928593/fullmiR-144/451dendritic cellinterferon-regulatory factor 5inflammatory bowel diseaseimmune regulation |
| spellingShingle | Zhijie Lin Zhijie Lin Xiaoyan Xie Min Gu Qian Chen Guotao Lu Xiaoqin Jia Weiming Xiao Jun Zhang Duonan Yu Weijuan Gong Weijuan Gong Weijuan Gong Weijuan Gong Weijuan Gong microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis Frontiers in Immunology miR-144/451 dendritic cell interferon-regulatory factor 5 inflammatory bowel disease immune regulation |
| title | microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis |
| title_full | microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis |
| title_fullStr | microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis |
| title_full_unstemmed | microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis |
| title_short | microRNA-144/451 decreases dendritic cell bioactivity via targeting interferon-regulatory factor 5 to limit DSS-induced colitis |
| title_sort | microrna 144 451 decreases dendritic cell bioactivity via targeting interferon regulatory factor 5 to limit dss induced colitis |
| topic | miR-144/451 dendritic cell interferon-regulatory factor 5 inflammatory bowel disease immune regulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.928593/full |
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