Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.

It is well established that female sex hormones have a pivotal role in inflammation. For instance, our group has previously reported that estradiol has proinflammatory actions during allergic lung response in animal models. Based on these findings, we have decided to further investigate whether T re...

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Autores principales: Ana Paula Ligeiro de Oliveira, Jean Pierre Schatzmann Peron, Adriana Lino Santos Franco, Beatriz Acceturi Golega, Rodolfo Paula Vieira, Olga Célia Martinez Ibanez, Orlando Garcia Ribeiro, Wafa Hanna Koury Cabrera, Marcelo De Franco, Ricardo Martins Oliveira-Filho, Luiz Vicente Rizzo, Bernardo Boris Vargaftig, Wothan Tavares de Lima
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:771ff4ed3d2b46bb8b49b75ec3a55fcd2021-11-18T07:41:34ZOvariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.1932-620310.1371/journal.pone.0065674https://doaj.org/article/771ff4ed3d2b46bb8b49b75ec3a55fcd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23799034/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203It is well established that female sex hormones have a pivotal role in inflammation. For instance, our group has previously reported that estradiol has proinflammatory actions during allergic lung response in animal models. Based on these findings, we have decided to further investigate whether T regulatory cells are affected by female sex hormones absence after ovariectomy. We evaluated by flow cytometry the frequencies of CD4(+)Foxp3(+) T regulatory cells (Tregs) in central and peripheral lymphoid organs, such as the thymus, spleen and lymph nodes. Moreover, we have also used the murine model of allergic lung inflammation a to evaluate how female sex hormones would affect the immune response in vivo. To address that, ovariectomized or sham operated female Balb/c mice were sensitized or not with ovalbumin 7 and 14 days later and subsequently challenged twice by aerosolized ovalbumin on day 21. Besides the frequency of CD4(+)Foxp3(+) T regulatory cells, we also measured the cytokines IL-4, IL-5, IL-10, IL-13 and IL-17 in the bronchoalveolar lavage from lungs of ovalbumine challenged groups. Our results demonstrate that the absence of female sex hormones after ovariectomy is able to increase the frequency of Tregs in the periphery. As we did not observe differences in the thymus-derived natural occurring Tregs, our data may indicate expansion or conversion of peripheral adaptive Tregs. In accordance with Treg suppressive activity, ovariectomized and ovalbumine-sensitized and challenged animals had significantly reduced lung inflammation. This was observed after cytokine analysis of lung explants showing significant reduction of pro-inflammatory cytokines, such as IL-4, IL-5, IL-13 and IL-17, associated to increased amount of IL-10. In summary, our data clearly demonstrates that OVA sensitization 7 days after ovariectomy culminates in reduced lung inflammation, which may be directly correlated with the expansion of Tregs in the periphery and further higher IL-10 secretion in the lungs.Ana Paula Ligeiro de OliveiraJean Pierre Schatzmann PeronAdriana Lino Santos FrancoBeatriz Acceturi GolegaRodolfo Paula VieiraOlga Célia Martinez IbanezOrlando Garcia RibeiroWafa Hanna Koury CabreraMarcelo De FrancoRicardo Martins Oliveira-FilhoLuiz Vicente RizzoBernardo Boris VargaftigWothan Tavares de LimaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65674 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ana Paula Ligeiro de Oliveira
Jean Pierre Schatzmann Peron
Adriana Lino Santos Franco
Beatriz Acceturi Golega
Rodolfo Paula Vieira
Olga Célia Martinez Ibanez
Orlando Garcia Ribeiro
Wafa Hanna Koury Cabrera
Marcelo De Franco
Ricardo Martins Oliveira-Filho
Luiz Vicente Rizzo
Bernardo Boris Vargaftig
Wothan Tavares de Lima
Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.
description It is well established that female sex hormones have a pivotal role in inflammation. For instance, our group has previously reported that estradiol has proinflammatory actions during allergic lung response in animal models. Based on these findings, we have decided to further investigate whether T regulatory cells are affected by female sex hormones absence after ovariectomy. We evaluated by flow cytometry the frequencies of CD4(+)Foxp3(+) T regulatory cells (Tregs) in central and peripheral lymphoid organs, such as the thymus, spleen and lymph nodes. Moreover, we have also used the murine model of allergic lung inflammation a to evaluate how female sex hormones would affect the immune response in vivo. To address that, ovariectomized or sham operated female Balb/c mice were sensitized or not with ovalbumin 7 and 14 days later and subsequently challenged twice by aerosolized ovalbumin on day 21. Besides the frequency of CD4(+)Foxp3(+) T regulatory cells, we also measured the cytokines IL-4, IL-5, IL-10, IL-13 and IL-17 in the bronchoalveolar lavage from lungs of ovalbumine challenged groups. Our results demonstrate that the absence of female sex hormones after ovariectomy is able to increase the frequency of Tregs in the periphery. As we did not observe differences in the thymus-derived natural occurring Tregs, our data may indicate expansion or conversion of peripheral adaptive Tregs. In accordance with Treg suppressive activity, ovariectomized and ovalbumine-sensitized and challenged animals had significantly reduced lung inflammation. This was observed after cytokine analysis of lung explants showing significant reduction of pro-inflammatory cytokines, such as IL-4, IL-5, IL-13 and IL-17, associated to increased amount of IL-10. In summary, our data clearly demonstrates that OVA sensitization 7 days after ovariectomy culminates in reduced lung inflammation, which may be directly correlated with the expansion of Tregs in the periphery and further higher IL-10 secretion in the lungs.
format article
author Ana Paula Ligeiro de Oliveira
Jean Pierre Schatzmann Peron
Adriana Lino Santos Franco
Beatriz Acceturi Golega
Rodolfo Paula Vieira
Olga Célia Martinez Ibanez
Orlando Garcia Ribeiro
Wafa Hanna Koury Cabrera
Marcelo De Franco
Ricardo Martins Oliveira-Filho
Luiz Vicente Rizzo
Bernardo Boris Vargaftig
Wothan Tavares de Lima
author_facet Ana Paula Ligeiro de Oliveira
Jean Pierre Schatzmann Peron
Adriana Lino Santos Franco
Beatriz Acceturi Golega
Rodolfo Paula Vieira
Olga Célia Martinez Ibanez
Orlando Garcia Ribeiro
Wafa Hanna Koury Cabrera
Marcelo De Franco
Ricardo Martins Oliveira-Filho
Luiz Vicente Rizzo
Bernardo Boris Vargaftig
Wothan Tavares de Lima
author_sort Ana Paula Ligeiro de Oliveira
title Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.
title_short Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.
title_full Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.
title_fullStr Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.
title_full_unstemmed Ovariectomized OVA-sensitized mice display increased frequency of CD4(+)Foxp3(+) T regulatory cells in the periphery.
title_sort ovariectomized ova-sensitized mice display increased frequency of cd4(+)foxp3(+) t regulatory cells in the periphery.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/771ff4ed3d2b46bb8b49b75ec3a55fcd
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