Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Jovanovic, Ivan, Radosavljevic, Gordana, Mitrovic, Maja, Lisnic Juranic, Vanda, McKenzie, Andrew N J, Arsenijevic, Nebojsa, Jonjic, Stipan, Lukic, Miodrag L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2011
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
_version_ 1782280794722533376
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
work_keys_str_mv AT jovanovicivan st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma
AT radosavljevicgordana st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma
AT mitrovicmaja st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma
AT lisnicjuranicvanda st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma
AT mckenzieandrewnj st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma
AT arsenijevicnebojsa st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma
AT jonjicstipan st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma
AT lukicmiodragl st2deletionenhancesinnateandacquiredimmunitytomurinemammarycarcinoma