AUTHOR=Hosseini Aref , Germic Nina , Markov Nikita , Stojkov Darko , Oberson Kevin , Yousefi Shida , Simon Hans-Uwe 

TITLE=The regulatory role of eosinophils in adipose tissue depends on autophagy

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1331151

DOI=10.3389/fimmu.2023.1331151

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Obesity is a metabolic condition that elevates the risk of all-cause mortality. Brown and beige adipose tissues, known for their thermogenic properties, offer potential therapeutic targets for combating obesity. Recent reports highlight the role of immune cells, including eosinophils, in adipose tissue homeostasis, while the underlying mechanisms are poorly understood.</p></sec><sec><title>Methods</title><p>To study the role of autophagy in eosinophils in this process, we used a genetic mouse model lacking autophagy-associated protein 5 (<italic>Atg5</italic>), specifically within the eosinophil lineage (<italic>Atg5</italic><sup>eoΔ</sup>).</p></sec><sec><title>Results</title><p>The absence of <italic>Atg5</italic> in eosinophils led to increased body weight, impaired glucose metabolism, and alterations in the cellular architecture of adipose tissue. Our findings indicate that <italic>Atg5</italic> modulates the functional activity of eosinophils within adipose tissue rather than their abundance. Moreover, RNA-seq analysis revealed upregulation of arginase 2 <italic>(Arg2)</italic> in <italic>Atg5</italic>-knockout eosinophils. Increased <italic>Arg2</italic> activity was shown to suppress adipocyte beiging. Furthermore, we observed enrichment of the purine pathway in the absence of <italic>Atg5</italic> in eosinophils, leading to a pro-inflammatory shift in macrophages and a further reduction in beiging.</p></sec><sec><title>Discussion</title><p>The data shed light on the importance of autophagy in eosinophils and its impact on adipose tissue homeostasis by suppressing <italic>Arg2</italic> expression and limiting inflammation in adipose tissue.</p></sec>