Unique adipose tissue invariant natural killer T cell subpopulations control adipocyte turnover in mice

Sang Mun Han, Eun Seo Park, Jeu Park, Hahn Nahmgoong, Yoon Ha Choi, Jiyoung Oh, Kyung Min Yim, Won Taek Lee, Yun Kyung Lee, Yong Geun Jeon, Kyung Cheul Shin, Jin Young Huh, Sung Hee Choi, Jiyoung Park, Jong Kyoung Kim () and Jae Bum Kim ()
Additional contact information
Sang Mun Han: Seoul National University
Eun Seo Park: DGIST
Jeu Park: Seoul National University
Hahn Nahmgoong: Seoul National University
Yoon Ha Choi: POSTECH
Jiyoung Oh: College of Information and Biotechnology, Ulsan National Institute of Science and Technology
Kyung Min Yim: Seoul National University
Won Taek Lee: Seoul National University
Yun Kyung Lee: Seoul National University College of Medicine & Seoul National University Bundang Hospital
Yong Geun Jeon: Seoul National University
Kyung Cheul Shin: Seoul National University
Jin Young Huh: Sogang University
Sung Hee Choi: Seoul National University College of Medicine & Seoul National University Bundang Hospital
Jiyoung Park: College of Information and Biotechnology, Ulsan National Institute of Science and Technology
Jong Kyoung Kim: POSTECH
Jae Bum Kim: Seoul National University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Adipose tissue invariant natural killer T (iNKT) cells are a crucial cell type for adipose tissue homeostasis in obese animals. However, heterogeneity of adipose iNKT cells and their function in adipocyte turnover are not thoroughly understood. Here, we investigate transcriptional heterogeneity in adipose iNKT cells and their hierarchy using single-cell RNA sequencing in lean and obese mice. We report that distinct subpopulations of adipose iNKT cells modulate adipose tissue homeostasis through adipocyte death and birth. We identify KLRG1+ iNKT cells as a unique iNKT cell subpopulation in adipose tissue. Adoptive transfer experiments showed that KLRG1+ iNKT cells are selectively generated within adipose tissue microenvironment and differentiate into a CX3CR1+ cytotoxic subpopulation in obese mice. In addition, CX3CR1+ iNKT cells specifically kill enlarged and inflamed adipocytes and recruit macrophages through CCL5. Furthermore, adipose iNKT17 cells have the potential to secrete AREG, and AREG is involved in stimulating adipose stem cell proliferation. Collectively, our data suggest that each adipose iNKT cell subpopulation plays key roles in the control of adipocyte turnover via interaction with adipocytes, adipose stem cells, and macrophages in adipose tissue.

Date: 2023
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DOI: 10.1038/s41467-023-44181-3

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