Senescent T Cell Induces Brown Adipose Tissue “Whitening” Via Secreting IFN-γ

• Main Authors: Xiao-Xi Pan, Kang-Li Yao, Yong-Feng Yang, Qian Ge, Run Zhang, Ping-Jin Gao, Cheng-Chao Ruan, Fang Wu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-03-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: senescence; T cell; adipose tissue; preadipocyte; brown adipocyte differentiation; IFN-γ
• Online Access: https://www.frontiersin.org/articles/10.3389/fcell.2021.637424/full

Aging-associated chronic inflammation is a key contributing factor to a cluster of chronic metabolic disorders, such as cardiovascular disease, obesity, and type 2 diabetes. Immune cells particularly T cells accumulate in adipose tissue with advancing age, and there exists a cross talk between T cell and preadipocyte, contributing to age-related adipose tissue remodeling. Here, we compared the difference in morphology and function of adipose tissue between young (3-month-old) and old (18-month-old) mice and showed the phenomenon of brown adipose tissue (BAT) “whitening” in old mice. Flow cytometry analysis suggested an increased proportion of T cells in BAT of old mice comparing with the young and exhibited senescent characteristics. We take advantage of coculture system to demonstrate directly that senescent T cells inhibited brown adipocyte differentiation of preadipocytes in adipose tissue. Mechanistically, both in vitro and in vivo studies suggested that senescent T cells produced and released a higher level of IFN-γ, which plays a critical role in inhibition of preadipocyte-to-brown adipocyte differentiation. Taken together, the data indicate that senescent T cell-derived IFN-γ is a key regulator in brown adipocyte differentiation.