Obesity-associated asthma was linked to increased adipose tissue perivascular and lymphoid-associated macrophages and reduced classical monocytes compared to obesity without asthma.
Case-Control (n=32)
Does asthma comorbidity alter adipose tissue inflammation and immune cell composition in adults with obesity?
Asthma comorbidity in obesity is associated with increased adipose tissue inflammation, suggesting asthma represents a systemic inflammatory process extending to adipose tissue.
Abstract Rationale Obesity increases asthma risk. The mechanisms by which obesity increases asthma prevalence and severity are unknown. Methods Single cell RNA sequencing of the immune-rich stromovascular fraction of subcutaneous adipose tissue was performed from 16 well-characterized adults with moderate-to-severe persistent, uncontrolled obesity-associated asthma and 16 adults with obesity but without asthma matched on age, sex, race, body mass index, and glycemic control status. Type 2 diabetes, systemic corticosteroid use in the prior 28 days, and use of any approved biologic for the treatment of asthma were exclusions. Single cell compositional data analysis (scCODA), pseudo-bulk and cell specific differential expression (DE) and gene set enrichment analysis (GSEA) of subcutaneous adipose tissue myeloid and T and NK cell compartments were compared. Results Adipose tissue donors were 75% female and 75% White in both cohorts. Matching on clinical parameters of age (49.5±14.1 and 50.0±14.4 years, asthma and asthma-free, respectively), BMI (38.7± 6.1 and 39.0±6.9 kg/m2, respectively), and A1c value (5.75±0.33 and 5.57±0.43%, respectively) was successful. Obese individuals with asthma show increased abundance of perivascular macrophages and lymphoid-associated macrophages (LAMs) and reduced abundance of classical monocytes and CD4 and CD8 naïve T cells in the adipose tissue compared to obese non-asthma individuals. These changes were mirrored by increased abundance in CD4 and CD8 memory and cytotoxic effector cell subsets. GSEA of pseudo-bulk DE identified upregulation of cellular metabolism, specifically oxidative phosphorylation, glycolysis, and fatty acid pathways, and decreased immune homeostatic pathways in asthma across the differentially abundant myeloid and T cell subsets. Cell type specific DE analysis of CD4 and CD8 T effector cell subtypes, LAMs, and perivascular macrophages identified significant induction of metallothionein gene expression in asthma, a signature previously associated with a combined T cell activation and exhaustion phenotype characteristic of immune cell dysfunction. Conclusions Adipose tissue from individuals with obesity-associated asthma is marked by increased tissue resident myeloid and T effector cell abundance, increased T cell and macrophage metabolic activity, and a dysfunctional activation signature. Asthma comorbidity further increases the adipose tissue inflammation observed in the context of obesity and suggests asthma represents a systemic inflammatory process extending to adipose tissue. This abstract is funded by: NIH U01AI155299, 5P30DK020593-48
Cahill et al. (Fri,) conducted a case-control in Obesity-associated asthma (n=32). Obesity-associated asthma vs. Obesity without asthma was evaluated on Single cell RNA sequencing of the immune-rich stromovascular fraction of subcutaneous adipose tissue. Obesity-associated asthma was linked to increased adipose tissue perivascular and lymphoid-associated macrophages and reduced classical monocytes compared to obesity without asthma.