Cell Metabolism
Volume 33, Issue 11, 2 November 2021, Pages 2277-2287.e5
Journal home page for Cell Metabolism

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

https://doi.org/10.1016/j.cmet.2021.08.004Get rights and content
Under an Elsevier user license
open archive

Highlights

  • ILC2s are lost during aging

  • Expanding aged ILC2s with IL-33 increases cold lethality in old mice

  • Adult ILC2s transferred into old mice are sufficient to rescue cold lethality

Summary

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.

Keywords

aging
adipose
ILC2
thermogenesis
IL-33
metabolism
inflammation

Data and code availability

  • RNA sequencing data reported in this paper was deposited to the Gene Expression Omnibus and accession numbers are listed in the key resources table.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

7

Lead contact