Ovariectomized OVA-Sensitized Mice Display Increased Frequency of CD4(+)Foxp3(+) T Regulatory Cells in the Periphery

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Ligeiro de Oliveira, Ana Paula ^[1] ; Schatzmann Peron, Jean Pierre ^[2] ; Santos Franco, Adriana Lino ^[3] ; Golega, Beatriz Acceturi ^[3] ; Vieira, Rodolfo Paula ^[1] ; Martinez Ibanez, Olga Celia ^[4] ; Ribeiro, Orlando Garcia ^[4] ; Koury Cabrera, Wafa Hanna ^[4] ; De Franco, Marcelo ^[4] ; Oliveira-Filho, Ricardo Martins ^[3] ; Rizzo, Luiz Vicente ^[5] ; Vargaftig, Bernardo Boris ^[3] ; de Lima, Wothan Tavares ^[3]

Afiliação do(s) autor(es)

^[1] Univ Nove de Julho UNINOVE, Programa Posgrad Biofoton Aplicada Ciencias Saude, Sao Paulo - Brazil

^[2] ICB USP, Dept Immunol, Sao Paulo - Brazil

^[3] ICB USP, Dept Pharmacol, Sao Paulo - Brazil

^[4] Butantan Inst, Immunogenet Lab, Sao Paulo - Brazil

^[5] HIAE, Inst Ensino & Pesquisa, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 6 JUN 17 2013.
• Citações Web of Science: 8

Resumo

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. (AU)

• Processo FAPESP: 09/51886-3 - Neuroimunomodulação: fármacos, estresse e citocinas nas relações entre os sistemas nervoso, endócrino e imune
• Beneficiário: João Palermo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/07208-0 - Modulação da inflamação pulmonar alérgica por adjuvantes ou tolerância imunológica
• Beneficiário: Momtchilo Russo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/18703-2 - O papel do eixo triptofano - Kinureninas na regulação da resposta imune através de receptores de glutamato tipo NMDA na encefalomielite experimental auto-imune e na lesão por isquemia e reperfusão cerebral
• Beneficiário: Jean Pierre Schatzmann Peron
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores