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Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models

Triptolide (TP) exerts a promising effect in the treatment of ulcerative colitis (UC). However, its toxicity seriously hinders its application in the clinic. Previous studies indicated that dendritic cells (DCs) are the main target through which TP exerts its immunoregulatory effect. Thus, we design...

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Autores principales: Rao, Quan, Ma, Guang-chao, Wu, Hao, Li, Meng, Xu, Wei, Wang, Guo-jun, Wang, Dong, Zhang, Cong-en, Ma, Zhi-jie, Zhang, Zhong-tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890574/
https://www.ncbi.nlm.nih.gov/pubmed/35225120
http://dx.doi.org/10.1080/10717544.2022.2044935
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author Rao, Quan
Ma, Guang-chao
Wu, Hao
Li, Meng
Xu, Wei
Wang, Guo-jun
Wang, Dong
Zhang, Cong-en
Ma, Zhi-jie
Zhang, Zhong-tao
author_facet Rao, Quan
Ma, Guang-chao
Wu, Hao
Li, Meng
Xu, Wei
Wang, Guo-jun
Wang, Dong
Zhang, Cong-en
Ma, Zhi-jie
Zhang, Zhong-tao
author_sort Rao, Quan
collection PubMed
description Triptolide (TP) exerts a promising effect in the treatment of ulcerative colitis (UC). However, its toxicity seriously hinders its application in the clinic. Previous studies indicated that dendritic cells (DCs) are the main target through which TP exerts its immunoregulatory effect. Thus, we designed an approach to target DCs in vitro to avoid the direct exposure of organs to TP. Our results revealed that DCs pretreated with TP (DCTP) exerted satisfactory therapeutic effects in mice with colitis, resulting in improved colonic inflammation and alleviated local lesion damage. In addition, no obvious toxicity was observed. DCTP also reshaped the immune milieu by decreasing CD4(+) T cell numbers and increasing regulatory T cell numbers in the spleen, mesenteric lymph nodes, peripheral blood and colon; these effects were further confirmed in vitro. Downregulation of CD80/86, ICAM-1, MHCI, TLR2/4, TNF-α, and IL-6 expression and upregulation of programmed cell death ligand 1 (PDL1) and IL-10 expression were observed, indicating that DCs were converted into tolerogenic DCs. In conclusion, DCTP can effectively reduce toxicity and alleviate colonic inflammation and local lesion damage in mice with colitis. The immune mechanism underlying the effects of DCTP included the conversion of DCs into tolerogenic DCs and the alteration of T cell differentiation to produce immunoinhibitory rather than immunostimulatory T cells.
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spelling pubmed-88905742022-03-03 Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models Rao, Quan Ma, Guang-chao Wu, Hao Li, Meng Xu, Wei Wang, Guo-jun Wang, Dong Zhang, Cong-en Ma, Zhi-jie Zhang, Zhong-tao Drug Deliv Research Article Triptolide (TP) exerts a promising effect in the treatment of ulcerative colitis (UC). However, its toxicity seriously hinders its application in the clinic. Previous studies indicated that dendritic cells (DCs) are the main target through which TP exerts its immunoregulatory effect. Thus, we designed an approach to target DCs in vitro to avoid the direct exposure of organs to TP. Our results revealed that DCs pretreated with TP (DCTP) exerted satisfactory therapeutic effects in mice with colitis, resulting in improved colonic inflammation and alleviated local lesion damage. In addition, no obvious toxicity was observed. DCTP also reshaped the immune milieu by decreasing CD4(+) T cell numbers and increasing regulatory T cell numbers in the spleen, mesenteric lymph nodes, peripheral blood and colon; these effects were further confirmed in vitro. Downregulation of CD80/86, ICAM-1, MHCI, TLR2/4, TNF-α, and IL-6 expression and upregulation of programmed cell death ligand 1 (PDL1) and IL-10 expression were observed, indicating that DCs were converted into tolerogenic DCs. In conclusion, DCTP can effectively reduce toxicity and alleviate colonic inflammation and local lesion damage in mice with colitis. The immune mechanism underlying the effects of DCTP included the conversion of DCs into tolerogenic DCs and the alteration of T cell differentiation to produce immunoinhibitory rather than immunostimulatory T cells. Taylor & Francis 2022-02-28 /pmc/articles/PMC8890574/ /pubmed/35225120 http://dx.doi.org/10.1080/10717544.2022.2044935 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Rao, Quan
Ma, Guang-chao
Wu, Hao
Li, Meng
Xu, Wei
Wang, Guo-jun
Wang, Dong
Zhang, Cong-en
Ma, Zhi-jie
Zhang, Zhong-tao
Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models
title Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models
title_full Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models
title_fullStr Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models
title_full_unstemmed Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models
title_short Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models
title_sort dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890574/
https://www.ncbi.nlm.nih.gov/pubmed/35225120
http://dx.doi.org/10.1080/10717544.2022.2044935
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