期刊
IMMUNOLOGY
卷 157, 期 3, 页码 268-279出版社
WILEY
DOI: 10.1111/imm.13081
关键词
asthma; follicular T cells; obesity; peripheral organs lymphoid
类别
资金
- Fundacao de Amparo a Pesquisa de Minas Gerais - FAPEMIG UNIVERSAL [2012/APQ 00535-12]
- Fundacao de Amparo a Pesquisa de Minas Gerais - FAPEMIG-PPM-Pesquisador Mineiro [00269-14]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq (Bolsa de Produtividade) [306575/2012-4, 306768/2015-1]
- CNPQ/PVE [401332/2014-4]
- Coordenacao de Aperfeicoamento Pessoal de Nivel Superior - CAPES
- Programa Pos Graduacao em Saude (PPGS) - Universidade Federal de Juiz de Fora. Juiz de Fora-MG, Brasil
- Programa de Pos Graduacao em Ciencias Biologicas (PPGCBio) - Universidade Federal de Juiz de Fora, Juiz de Fora - MG, Brasil
Asthma and obesity present rising incidence, and their concomitance is a reason for concern, as obese individuals are usually resistant to conventional asthma treatments and have more exacerbation episodes. Obesity affects several features in the lungs during asthma onset, shifting the T helper type 2 (Th2)/eosinophilic response towards a Th17/neutrophilic profile. Moreover, those individuals can present reduced atopy and delayed cytokine production. However, the impact of obesity on follicular helper T (Tfh) cells and B cells that could potentially result in antibody production disturbances are still unclear. Therefore, we aimed to assess the peripheral response to ovalbumin (OVA) in a concomitant model of obesity and asthma. Pulmonary allergy was induced, in both lean and obese female BALB/c mice, through OVA sensitizations and challenges. Mediastinal lymph nodes (MLNs) and spleen were processed for immunophenotyping. Lung was used for standard allergy analysis. Obese-allergic mice produced less anti-OVA IgE and more IgG2a than lean-allergic mice. Dendritic cells (CD11c(+)MHCII(high)) expressed less CD86 and more PDL1 in obese-allergic mice compared with lean-allergic mice, in the MLNs. Meanwhile, B cells (CD19(+)CD40(+)) were more frequent and the amount of PDL1/PD1(+) cells was diminished by obesity, with the opposite effects in the spleen. Tfh cells (CD3(+)CD4(+)CXCR5(+)PD1(+)) expressing FoxP3 were more frequent in obese mice, associated with the predominance of Th (CD3(+)CD4(+)) cells expressing interleukin-4/GATA3 in the MLNs and interleukin-17A/ROR gamma T in the spleen. Those modifications to the main components of the germinal centers could be resulting in the increased IgG2a production, which-associated with the Th17/neutrophilic profile-contributes to asthma worsening and represents an important target for future treatment strategies.
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