Details

Autor(en) / Beteiligte

• Esteves de Oliveira, Erick
• Castro e Silva, Flávia Márcia
• Caçador Ayupe, Marina
• Gomes Evangelista Ambrósio, Marcilene
• Passos de Souza, Viviane
• Costa Macedo, Gilson
• Ferreira, Ana Paula

Titel

Obesity affects peripheral lymphoid organs immune response in murine asthma model

Ist Teil von

• Immunology, 2019-07, Vol.157 (3), p.268-279

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2019

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Summary 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+ MHCIIhigh) 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/RORγT 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. We have demonstrated that obesity affects the allergic immune response in the lungs, and the serum IgE and IgG2a titers; these alterations were accompanied by modifications in the peripheral lymphoid organs. Mediastinal lymph nodes presented a greater B‐cell population, together with increased frequency of follicular regulatory T cells and interleukin‐4‐producing T helper cells. Meanwhile, there was a reduction of the splenic B‐cell frequency of obese‐allergic animals, and the intensification of a T helper type 17 profile.