Obesity affects peripheral lymphoid organs immune response in murine asthma model.
Erick Esteves de OliveiraFlávia Márcia de Castro E SilvaMarina Caçador AyupeMarcilene Gomes Evangelista AmbrósioViviane Passos de SouzaGilson Costa MacedoAna Paula FerreiraPublished in: Immunology (2019)
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.
Keyphrases
- high fat diet induced
- weight loss
- metabolic syndrome
- insulin resistance
- allergic rhinitis
- chronic obstructive pulmonary disease
- induced apoptosis
- type diabetes
- dendritic cells
- adipose tissue
- lung function
- immune response
- cell cycle arrest
- weight gain
- lymph node
- bariatric surgery
- regulatory t cells
- cell death
- atopic dermatitis
- wild type
- physical activity
- bone mineral density
- early stage
- inflammatory response
- intensive care unit
- cystic fibrosis
- oxidative stress
- skeletal muscle
- endothelial cells
- body mass index
- drug induced
- acute respiratory distress syndrome
- current status
- pi k akt