IL-4 signaling modulates sympathetic innervation in white adipose tissue Yixuan Wu1, Ajay Chawla1* 1University of California, San Francisco *Corresponding Author
In the central nervous system (CNS), type 2 cytokines, such as interleukin-4 (IL-4), modulate neuronal development and homeostasis via their actions on neurons and resident myeloid cells. However, the functions of type 2 cytokines in maintenance of peripheral nerves remain poorly understood. Since previous studies have implicated neuroimmune interactions in physiologic adaptations of white adipose tissue (WAT) to environmental challenges, we hypothesized that type 2 cytokines modulate the innervation or activity of the sympathetic nervous system (SNS) in WAT.
To study these neuroimmune interactions, we used gain- and loss-of-function approaches coupled with Adipo Clear (a modified iDISCO protocol) and light sheet microscopy to map sympathetic innervation and beige adipocyte development in WAT. We found that physiologic development of beige adipocytes in WAT required type 2 cytokines IL-4/13 and their signaling receptor IL-4Ra. Conversely, treatment of obese mice with IL-4 complex reduced adiposity and body weight, which were associated with increased sympathetic innervation and recruitment of beige adipocytes.
Studies are on-going to identify the underlying mechanisms by which type 2 cytokines and immune cells modulate the growth and activity of sympathetic nerves in WAT. Our work not only has important implications for obesity, a disease associated with decreased SNS activity, but also raise the possibility that type 2 immune pathways might be exploited to promote growth of peripheral nerves after injury or damage.
Funding: NIH/NIDDK, Agency for Science, Technology and Research (Singapore)
Credits: None available.
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