Background: Eosinophilic oesophagitis (EoE) is an emergent chronic immunemediated disease of the oesophagus, which affects both children and adults. It is clinically characterized by dysphagia, food impaction and oesophageal eosinophilia.Epidemiological studies indicate that obesity can worsen allergic symptoms; however, its effect on EoE immunopathological response has not been evaluated yet. This study aimed to assess the effect of obesity on allergic inflammation and T helper-2 profile in an EoE experimental model. Methods:Obesity was induced by high-fat feeding. After 7 weeks of diet, male BALB/c mice were subcutaneously sensitized and orally challenged with OVA.Results: Obesity itself induced a significant mast cell and eosinophil accumulation in the oesophagus, trachea, gut and lung. After allergy induction, this number was higher, when compared to lean-allergic mice. Moreover, obese-allergic mice showed higher remodelling area, in the oesophagus, associated with higher IL-5 and TSLP mRNA expression.In contrast, FoxP3 and IL-10 were less expressed in comparison with lean-allergic mice.In addition, the amount of CD11c + MHCII + PDL1 + dendritic cells was reduced, while the number of CD11c + MHCII + CD80 + DCs and CD3 + CD4 + GATA 3 + IL-4 + cells was increased in obese-allergic mice in the spleen and lymph nodes when compared to lean-allergic mice. Conclusion:Obesity aggravated the immune histopathological characteristics in the EoE experimental model, which was associated with the reduction in the regulatory profile, and the increased inflammatory cells influx, related to the T H 2 profile.Altogether, the data provide new knowledge about obesity as a risk factor, worsening EoE symptoms, and contribute for future treatment strategies for this specific profile. K E Y W O R D Sallergy, eosinophilic oesophagitis, immune response, inflammation, obesity | 245 SILVA et AL.

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.

No abstract

No abstract

No abstract