Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity

Hongdong Wang, Lei Shen, Xitai Sun, Fangcen Liu, Wenhuan Feng, Chunping Jiang, Xuehui Chu, Xiao Ye, Can Jiang, Yan Wang, Pengzi Zhang, Mengwei Zang, Dalong Zhu and Yan Bi ()
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Hongdong Wang: Drum Tower Hospital Affiliated to Nanjing University Medical School
Lei Shen: Shanghai Jiao Tong University School of Medicine
Xitai Sun: Drum Tower Hospital Affiliated to Nanjing University Medical School
Fangcen Liu: Drum Tower Hospital Clinical College of Nanjing Medical University
Wenhuan Feng: Drum Tower Hospital Affiliated to Nanjing University Medical School
Chunping Jiang: Drum Tower Hospital Affiliated to Nanjing University Medical School
Xuehui Chu: Drum Tower Hospital Affiliated to Nanjing University Medical School
Xiao Ye: Drum Tower Hospital Clinical College of Nanjing Medical University
Can Jiang: Drum Tower Hospital Affiliated to Nanjing University Medical School
Yan Wang: Drum Tower Hospital Affiliated to Nanjing University Medical School
Pengzi Zhang: Drum Tower Hospital Affiliated to Nanjing University Medical School
Mengwei Zang: University of Texas Health San Antonio
Dalong Zhu: Drum Tower Hospital Affiliated to Nanjing University Medical School
Yan Bi: Drum Tower Hospital Affiliated to Nanjing University Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c+ macrophage activation. Reconstruction of the adipose ILC1 population in Prkdc−/−IL2rg−/− mice by adoptive transfer drives adipose fibrogenesis through activation of TGFβ1 signaling; however, transfer of Ifng−/− ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.

Date: 2019
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DOI: 10.1038/s41467-019-11270-1

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