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; Yan Bi

doi:10.1038/s41467-019-11270-1

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, Yan Bi

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

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.

Original language	English (US)
Article number	3254
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11270-1
State	Published - Dec 1 2019

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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@article{3bd29df28c404820859b99008e5558cc,

title = "Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity",

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.",

author = "Hongdong Wang and Lei Shen and Xitai Sun and Fangcen Liu and Wenhuan Feng and Chunping Jiang and Xuehui Chu and Xiao Ye and Can Jiang and Yan Wang and Pengzi Zhang and Mengwei Zang and Dalong Zhu and Yan Bi",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China Grant Awards (81770819, 81570737, 81370947, 81570736, 81500612, 81400832, 81600637, 81600632, and 81703294), the National Key Research and Development Program of China (2016YFC1304804 and 2017YFC1309605), the Jiangsu Provincial Key Medical Discipline (ZDXKB2016012), the Key Project of Nanjing Clinical Medical Science, Jiangsu Province Key Research and Development Program (BE2016606), the Jiangsu Provincial Medical Talent (ZDRCA2016062), the Natural Science Foundation of Jiangsu Province of China (BK20170125), the Scientific Research Foundation of “Project 333” in Jiangsu Province (GYHT20190013), the Jiangsu Provincial Medical Youth Talent (QNRC2016020, QNRC2016019, and QNRC2016018), the Medical Scientific Research Foundation of Jiangsu Province of China (Z201610 and Q2017006), the Science and Technology Project of Administration of Traditional Chinese Medicine of Jiangsu Province of China (YB2015072), the Six Talent Peaks Project of Jiangsu Province of China (WSN-165 and SWYY-091), the Fundamental Research Funds for the Central Universities (021414380444, 021414380092, 021414380208, 021414380160, 021414380142, 021414380279, 021414380296, and 021414380317), the Nanjing Science and Technology Development Project (ZKX16036, YKK16105, and 201605019), and the Nanjing Health Youth Talent (QRX17123). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-11270-1",

language = "English (US)",

volume = "10",

journal = "Nature communications",

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TY - JOUR

T1 - Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity

AU - Wang, Hongdong

AU - Shen, Lei

AU - Sun, Xitai

AU - Liu, Fangcen

AU - Feng, Wenhuan

AU - Jiang, Chunping

AU - Chu, Xuehui

AU - Ye, Xiao

AU - Jiang, Can

AU - Wang, Yan

AU - Zhang, Pengzi

AU - Zang, Mengwei

AU - Zhu, Dalong

AU - Bi, Yan

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China Grant Awards (81770819, 81570737, 81370947, 81570736, 81500612, 81400832, 81600637, 81600632, and 81703294), the National Key Research and Development Program of China (2016YFC1304804 and 2017YFC1309605), the Jiangsu Provincial Key Medical Discipline (ZDXKB2016012), the Key Project of Nanjing Clinical Medical Science, Jiangsu Province Key Research and Development Program (BE2016606), the Jiangsu Provincial Medical Talent (ZDRCA2016062), the Natural Science Foundation of Jiangsu Province of China (BK20170125), the Scientific Research Foundation of “Project 333” in Jiangsu Province (GYHT20190013), the Jiangsu Provincial Medical Youth Talent (QNRC2016020, QNRC2016019, and QNRC2016018), the Medical Scientific Research Foundation of Jiangsu Province of China (Z201610 and Q2017006), the Science and Technology Project of Administration of Traditional Chinese Medicine of Jiangsu Province of China (YB2015072), the Six Talent Peaks Project of Jiangsu Province of China (WSN-165 and SWYY-091), the Fundamental Research Funds for the Central Universities (021414380444, 021414380092, 021414380208, 021414380160, 021414380142, 021414380279, 021414380296, and 021414380317), the Nanjing Science and Technology Development Project (ZKX16036, YKK16105, and 201605019), and the Nanjing Health Youth Talent (QRX17123). Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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

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