Obesity affects peripheral lymphoid organs immune response in murine asthma model

Abstract

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.

The onset, development and pathogenesis of severe neutrophilic asthma

“…Obesity plays a role in aggravating asthma symptoms. A high‐fat diet increases the body weight of asthmatic mice 5,6,95 and further increases allergen‐induced neutrophilic airway inflammation, airway hyperresponsiveness, cupped cell proliferation, tissue remodeling, the production of cytokines (i.e. IL‐17A, IL‐1β and macrophage inflammatory protein‐2), and the level of MPO in the lungs 6,95,96 .…”

“…IL‐17A, IL‐1β and macrophage inflammatory protein‐2), and the level of MPO in the lungs 6,95,96 . In addition, obesity increases the IL17A + / RORγT + Th cell population in the spleen of asthma mice, 5 which is associated with neutrophilic inflammation and leads to a worsening of asthma symptoms. Asthma patients with an elevated visceral fat area have elevated total leukocytes, fewer eosinophils, and increased IL‐6 and IL‐8 in the sputum 97 .…”

Adipocyte inflammation and pathogenesis of viral pneumonias: an overlooked contribution

“…B cells that reside within AT are skewed toward a pro-inflammatory state during obesity, a state that limits their effector function and capabilities to produce antibodies. 173 , 174 Obesity also decreases the numbers and diminishes activation of T follicular helper cells in peripheral lymphoid organs, 175 potentially impacting proper development of mature B Cells. Finally, metabolism plays an important regulatory role in shaping the humoral immune response.…”

Structural changes of the spleen in experimental obesity

“…In the current scientific literature there is not enough information about the effect of obesity on the immune (lymphoid) organs, which provide protection of the body against foreign antigens. Adipose tissue is a complex endocrine organ whose effect on organs and tissues is significant and diverse, increasing the likelihood of multiple diseases [9,15,18,20]. Investigations into the dynamics of changes in the structural organization of organs and tissues, as well as possible methods for their correction, remain relevant and important for both theoretical and practical medicine.…”