Identification of Adipose-Specific iNKT Cell Subpopulation through Single-Cell RNA Sequencing

Abstract

Invariant natural killer T (iNKT) cells are innate T cells that recognize CD1d-loaded lipid antigens. In adipose tissue, iNKT cells contribute to maintenance of adipose tissue homeostasis through active communication with CD1d-positive adipocytes. By recognizing lipid antigens, adipose iNKT cells kill harmful cells, such as hypertrophic adipocytes and pro-inflammatory macrophages, and promote stem cell proliferation. These characteristics seem not to be observed in hepatic or splenic iNKT cells. However, it has not been thoroughly understood how adipose iNKT cells control cell fates in adipose tissue. Here, we adopted single-cell RNA sequencing to identify unique subpopulations of adipose iNKT cells involved in the clearance of deleterious cells or stem cell renewal. Adipose iNKT cells were largely categorized into 3 subpopulations; iNKT1A, iNKT1B, and iNKT17. Transcriptome analysis revealed that iNKT1A cells were the adipose-specific subpopulation, while iNKT1B and iNKT17 cells were similar to splenic and thymic iNKT cells. Moreover, adoptive transfer experiments showed that iNKT1A cells were generated only in adipose tissue, but not in other organs, indicating that adipose tissue microenvironment plays crucial roles for generation of iNKT1A cells. Collectively, our data showed that iNKT1A cells would be the adipose-specific iNKT subpopulation and could be generated by adipose tissue microenvironment. © FASEB.