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Obesity affects peripheral lymphoid organs immune response in murine asthma model
Author(s) -
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
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13081
Subject(s) - immunology , medicine , immunoglobulin e , foxp3 , germinal center , allergy , immune system , b cell , antibody
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 ( Th 2)/eosinophilic response towards a Th 17/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 ( MLN s) 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 ( CD 11c + MHCII high ) expressed less CD 86 and more PDL 1 in obese‐allergic mice compared with lean‐allergic mice, in the MLN s. Meanwhile, B cells ( CD 19 + CD 40 + ) were more frequent and the amount of PDL 1/ PD 1 + cells was diminished by obesity, with the opposite effects in the spleen. Tfh cells ( CD 3 + CD 4 + CXCR 5 + PD 1 + ) expressing FoxP3 were more frequent in obese mice, associated with the predominance of Th ( CD 3 + CD 4 + ) cells expressing interleukin‐4/ GATA 3 in the MLN s and interleukin‐17A/ ROR γ 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 Th 17/neutrophilic profile – contributes to asthma worsening and represents an important target for future treatment strategies.