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ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma
ST2 is a member of the IL-1 receptor family and IL-33 was recently identified as its natural ligand. The IL-33/ST2 pathway regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions, but the role of ST2 signaling in tumor growth and metastasis has not been investigated. We aimed to...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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WILEY-VCH Verlag
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746127/ https://www.ncbi.nlm.nih.gov/pubmed/21484786 http://dx.doi.org/10.1002/eji.201141417 |
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author | Jovanovic, Ivan Radosavljevic, Gordana Mitrovic, Maja Lisnic Juranic, Vanda McKenzie, Andrew N J Arsenijevic, Nebojsa Jonjic, Stipan Lukic, Miodrag L |
author_facet | Jovanovic, Ivan Radosavljevic, Gordana Mitrovic, Maja Lisnic Juranic, Vanda McKenzie, Andrew N J Arsenijevic, Nebojsa Jonjic, Stipan Lukic, Miodrag L |
author_sort | Jovanovic, Ivan |
collection | PubMed |
description | ST2 is a member of the IL-1 receptor family and IL-33 was recently identified as its natural ligand. The IL-33/ST2 pathway regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions, but the role of ST2 signaling in tumor growth and metastasis has not been investigated. We aimed to investigate whether ST2 gene deletion affects tumor appearance, growth, and metastasis, and antitumor immunity in an experimental metastatic breast cancer model. Deletion of ST2 in BALB/c mice bearing mammary carcinoma attenuated tumor growth and metastasis, which was accompanied by increased serum levels of IL-17, IFN-γ, and TNF-α and decreased IL-4. Tumor-bearing ST2(−/−) mice had significantly higher percentages of activated CD27(high)CD11b(high) NK cells, CD69(+) and KLRG(−) NK cells and higher cytotoxic activity of splenocytes, NK cells, and CD8(+) T cells in vitro. A significantly higher number of NK cells expressing IFN-γ were found in ST2(−/−) mice compared with WT recipients. In vivo depletion of CD8(+) or NK cells revealed a key role for NK cells in enhanced antitumor immunity in ST2(−/−) mice. We report for the first time that suppressed breast cancer progression and metastasis in mice lacking ST2 corresponds mainly with enhanced cytotoxic activity of NK cells, and increased systemic Th1/Th17 cytokines. |
format | Online Article Text |
id | pubmed-3746127 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | WILEY-VCH Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-37461272013-08-20 ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma Jovanovic, Ivan Radosavljevic, Gordana Mitrovic, Maja Lisnic Juranic, Vanda McKenzie, Andrew N J Arsenijevic, Nebojsa Jonjic, Stipan Lukic, Miodrag L Eur J Immunol Cellular Immune Response ST2 is a member of the IL-1 receptor family and IL-33 was recently identified as its natural ligand. The IL-33/ST2 pathway regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions, but the role of ST2 signaling in tumor growth and metastasis has not been investigated. We aimed to investigate whether ST2 gene deletion affects tumor appearance, growth, and metastasis, and antitumor immunity in an experimental metastatic breast cancer model. Deletion of ST2 in BALB/c mice bearing mammary carcinoma attenuated tumor growth and metastasis, which was accompanied by increased serum levels of IL-17, IFN-γ, and TNF-α and decreased IL-4. Tumor-bearing ST2(−/−) mice had significantly higher percentages of activated CD27(high)CD11b(high) NK cells, CD69(+) and KLRG(−) NK cells and higher cytotoxic activity of splenocytes, NK cells, and CD8(+) T cells in vitro. A significantly higher number of NK cells expressing IFN-γ were found in ST2(−/−) mice compared with WT recipients. In vivo depletion of CD8(+) or NK cells revealed a key role for NK cells in enhanced antitumor immunity in ST2(−/−) mice. We report for the first time that suppressed breast cancer progression and metastasis in mice lacking ST2 corresponds mainly with enhanced cytotoxic activity of NK cells, and increased systemic Th1/Th17 cytokines. WILEY-VCH Verlag 2011-07 2011-04-12 /pmc/articles/PMC3746127/ /pubmed/21484786 http://dx.doi.org/10.1002/eji.201141417 Text en Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Cellular Immune Response Jovanovic, Ivan Radosavljevic, Gordana Mitrovic, Maja Lisnic Juranic, Vanda McKenzie, Andrew N J Arsenijevic, Nebojsa Jonjic, Stipan Lukic, Miodrag L ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma |
title | ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma |
title_full | ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma |
title_fullStr | ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma |
title_full_unstemmed | ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma |
title_short | ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma |
title_sort | st2 deletion enhances innate and acquired immunity to murine mammary carcinoma |
topic | Cellular Immune Response |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746127/ https://www.ncbi.nlm.nih.gov/pubmed/21484786 http://dx.doi.org/10.1002/eji.201141417 |
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