Tissue specific imprinting on innate lymphoid cells during homeostasis and disease process revealed by integrative inference of single-cell transcriptomics

Peng Song; Ke Cao; Yonghuan Mao; Shichao Ai; Feng Sun; Qiongyuan Hu; Song Liu; Meng Wang; Xiaofeng Lu; Wenxian Guan; Xiaofei Shen

doi:10.3389/fimmu.2023.1127413

Tissue specific imprinting on innate lymphoid cells during homeostasis and disease process revealed by integrative inference of single-cell transcriptomics

Front Immunol. 2023 Mar 7:14:1127413. doi: 10.3389/fimmu.2023.1127413. eCollection 2023.

Authors

Peng Song^{1

2}, Ke Cao³, Yonghuan Mao^{1

2}, Shichao Ai¹, Feng Sun¹, Qiongyuan Hu¹, Song Liu¹, Meng Wang¹, Xiaofeng Lu¹, Wenxian Guan¹, Xiaofei Shen^{1

2}

Affiliations

¹ Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
² Department of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
³ Department of Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Abstract

Introduction: Innate lymphoid cells (ILCs) are key components of the immune system, yet the similarity and distinction of the properties across tissues under homeostasis, inflammation and tumor process remain elusive.

Methods: Here we performed integrative inference of ILCs to reveal their transcriptional profiles and heterogeneity from single-cell genomics. We collected a large number of ILCs from human six different tissues which can represent unique immune niches (circulation, lymphoid tissue, normal and inflamed mucosa, tumor microenvironment), to systematically address the transcriptional imprinting.

Results: ILCs are profoundly imprinted by their organ of residence, and tissue-specific distinctions are apparent under pathological conditions. In the hepatocellular carcinoma microenvironment, we identified intermediate c-kit⁺ ILC2 population, and lin^-CD127^- NK-like cells that expressed markers of cytotoxicity including CCL5 and IFNG. Additionally, CD127⁺CD94⁺ ILC1s were preferentially enriched in inflamed ileum from patients with Crohn's disease.

Discussion: These analyses depicted a comprehensive characterization of ILC anatomical distribution and subset heterogeneity, and provided a base line for future temporal or spatial studies focused on tissue-specific ILC-mediated immunity.

Keywords: cell heterogeneity; innate lymphoid cells; integrative inference; single-cell transcriptomics; tissue imprinting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Homeostasis
Humans
Immunity, Innate*
Inflammation
Lymphocytes*
Transcriptome

Grants and funding

This work was supported by National Natural Science Foundation of China (81970500 XS, 82172645 WG, 82002082 KC), Start-up funding for the introduction of talents in Nanjing Drum Tower Hospital (RC2022-015, XS).