Adipose eosinophils promote alternatively activated macrophages that maintain metabolic homeostasis (151.21)

• Published in: The Journal of immunology (1950) 2011-04, Vol.186 (1_Supplement), p.151-151.21
• Main Authors: Molofsky, Ari, Wu, Davina, Liang, Hong-Erh, Bando, Jennifer, Jouihan, Hani, Ricardo-Gonzalez, Robert, Chawla, Ajay, Locksley, Richard
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.186.Supp.151.21

Eosinophils are innate Th2-related granulocytes that are elevated in asthma, allergy, and helminth infection, and are frequency associated with alternatively activated macrophages (AAMs). Whereas adipose classically activated macrophages are associated with obesity and type-2 diabetes, AAM help maintain ‘lean physiology’. Adipose AAM can be induced by the cytokine interleukin-4 (IL-4), although a definitive cellular source of IL-4 within adipose tissue is not known. Surprisingly, we find eosinophils are resident within mouse white adipose tissues, where they are the major interleukin-4 (IL-4) expressing cells. Elevated adipose eosinophils promote Arginase-1+ AAM in an IL-4/13 dependent manner, and, in the absence of eosinophils or IL-4/IL-13, adipose AAM are diminished. In mouse models of obesity, adipose eosinophils inversely correlate with weight, and a genetic absence of eosinophils results in increased body fat and insulin resistance. Conversely, infection with the helminth Nippostrongylus brasiliensis leads to prolonged adipose eosinophilia and decreased insulin resistance. Eosinophils are evolutionarily conserved cells whose function has remained elusive, present in high levels in many naturally parasitized human populations. We speculate that eosinophils participate in integrating metabolic and immune signals to maintain homeostasis during chronic parasitism.