RT Journal Article
SR Electronic
T1 Dysregulation of adipose ILC2 underlies thermogenic failure in aging
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.08.288431
DO 10.1101/2020.09.08.288431
A1 Emily L. Goldberg
A1 Irina Shchukina
A1 Yun-Hee Youm
A1 Christina D. Camell
A1 Tamara Dlugos
A1 Maxim N. Artyomov
A1 Vishwa Deep Dixit
YR 2020
UL http://biorxiv.org/content/early/2020/09/08/2020.09.08.288431.abstract
AB 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 aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2) 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 cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2 are sufficient to protect old mice against cold. Thus, the functional defects in adipose ILC2 during aging drive thermogenic failure.One Sentence Summary Age-related changes in adipose tissue drive reprogramming of ILC2 that leads to impaired cold toleranceCompeting Interest StatementThe authors have declared no competing interest.