IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2

Emily L. Goldberg, Irina Shchukina, Yun Hee Youm, Seungjin Ryu, Takeshi Tsusaka, Kyrlia C. Young, Christina D. Camell, Tamara Dlugos, Maxim N. Artyomov, Vishwa Deep Dixit

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Aging impairs the integrated immunometabolic responses, which have evolved to maintain core body temperature in homeotherms to survive cold stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response, but how adipose tissue-resident cells instigate thermogenic failure in the aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2s) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and increased cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2s are sufficient to protect old mice against cold. Thus, the functional defects in adipose ILC2s during aging drive thermogenic failure.

Original languageEnglish (US)
Pages (from-to)2277-2287.e5
JournalCell Metabolism
Issue number11
StatePublished - Nov 2 2021

Bibliographical note

Funding Information:
We thank all members of the Dixit lab for critical discussion and feedback related to this project. All schematics were created with . The Dixit lab is supported in part by NIH grants P01AG051459 , AR070811 , and AG068863 and Cure Alzheimer’s Fund . The Goldberg Lab is supported in part by the National Institute on Aging ( R00AG058801 ). T.T. is supported by a postdoctoral fellowship from the Japan Society for the Promotion of Science .

Publisher Copyright:
© 2021


  • IL-33
  • ILC2
  • adipose
  • aging
  • inflammation
  • metabolism
  • thermogenesis


Dive into the research topics of 'IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2'. Together they form a unique fingerprint.

Cite this