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Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice

BACKGROUND: Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compar...

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Autores principales: Ni, Guoying, Liao, Zaowen, Chen, Shu, Wang, Tianfang, Yuan, Jianwei, Pan, Xuan, Mounsey, Kate, Cavezza, Shelley, Liu, Xiaosong, Wei, Ming Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557397/
https://www.ncbi.nlm.nih.gov/pubmed/28810829
http://dx.doi.org/10.1186/s12865-017-0224-x
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author Ni, Guoying
Liao, Zaowen
Chen, Shu
Wang, Tianfang
Yuan, Jianwei
Pan, Xuan
Mounsey, Kate
Cavezza, Shelley
Liu, Xiaosong
Wei, Ming Q.
author_facet Ni, Guoying
Liao, Zaowen
Chen, Shu
Wang, Tianfang
Yuan, Jianwei
Pan, Xuan
Mounsey, Kate
Cavezza, Shelley
Liu, Xiaosong
Wei, Ming Q.
author_sort Ni, Guoying
collection PubMed
description BACKGROUND: Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut. Blocking IL-10 at the time of immunization may result in unwanted side effects, especially immune-pathological diseases in the intestine. METHODS: We investigated whether blocking IL-10 at the time of immunization results in intestinal inflammation responses in a mouse TC-1 tumour model and in a NOD autoimmune disease prone mouse model. RESULTS: We now show that blocking IL-10 at the time of immunization increases IL-10 production by CD4+ T cells in the spleen and draining lymph nodes, and does not result in blood cell infiltration to the intestines leading to intestinal pathological changes. Moreover, immunization with papillomavirus like particles combined with simultaneously blocking IL-10 signalling does not increase the incidence of autoimmune disease in Non-obese diabetic (NOD) mice. CONCLUSIONS: Our results indicate that immunization with an IL-10 inhibitor may facilitate the generation of safe, effective therapeutic vaccines against chronic viral infection and cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-017-0224-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-55573972017-08-16 Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice Ni, Guoying Liao, Zaowen Chen, Shu Wang, Tianfang Yuan, Jianwei Pan, Xuan Mounsey, Kate Cavezza, Shelley Liu, Xiaosong Wei, Ming Q. BMC Immunol Research Article BACKGROUND: Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut. Blocking IL-10 at the time of immunization may result in unwanted side effects, especially immune-pathological diseases in the intestine. METHODS: We investigated whether blocking IL-10 at the time of immunization results in intestinal inflammation responses in a mouse TC-1 tumour model and in a NOD autoimmune disease prone mouse model. RESULTS: We now show that blocking IL-10 at the time of immunization increases IL-10 production by CD4+ T cells in the spleen and draining lymph nodes, and does not result in blood cell infiltration to the intestines leading to intestinal pathological changes. Moreover, immunization with papillomavirus like particles combined with simultaneously blocking IL-10 signalling does not increase the incidence of autoimmune disease in Non-obese diabetic (NOD) mice. CONCLUSIONS: Our results indicate that immunization with an IL-10 inhibitor may facilitate the generation of safe, effective therapeutic vaccines against chronic viral infection and cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-017-0224-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-15 /pmc/articles/PMC5557397/ /pubmed/28810829 http://dx.doi.org/10.1186/s12865-017-0224-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ni, Guoying
Liao, Zaowen
Chen, Shu
Wang, Tianfang
Yuan, Jianwei
Pan, Xuan
Mounsey, Kate
Cavezza, Shelley
Liu, Xiaosong
Wei, Ming Q.
Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice
title Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice
title_full Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice
title_fullStr Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice
title_full_unstemmed Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice
title_short Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice
title_sort blocking il-10 signalling at the time of immunization does not increase unwanted side effects in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557397/
https://www.ncbi.nlm.nih.gov/pubmed/28810829
http://dx.doi.org/10.1186/s12865-017-0224-x
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