CD16+ monocytes are involved in the hyper-inflammatory state of Prader-Willi Syndrome by single-cell transcriptomic analysis

Yunyun Xu; Xu Hou; Honglin Guo; Zhenyu Yao; Xiude Fan; Chao Xu; Guimei Li; Yanzhou Wang; Yan Sun; Ling Gao; Yongfeng Song; Jiajun Zhao

doi:10.3389/fimmu.2023.1153730

CD16⁺ monocytes are involved in the hyper-inflammatory state of Prader-Willi Syndrome by single-cell transcriptomic analysis

Front Immunol. 2023 May 11:14:1153730. doi: 10.3389/fimmu.2023.1153730. eCollection 2023.

Authors

Yunyun Xu^{1

2

3

4

5}, Xu Hou^{2

6}, Honglin Guo^{3

4

5}, Zhenyu Yao^{2

3

4

5}, Xiude Fan^{2

3

4

5}, Chao Xu^{2

3

4

5}, Guimei Li⁷, Yanzhou Wang⁸, Yan Sun⁷, Ling Gao^{4

9}, Yongfeng Song^{1

2

3

4

5}, Jiajun Zhao^{1

2

3

4

5

6}

Affiliations

¹ Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, China.
² Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
³ Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, China.
⁴ Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, China.
⁵ Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Jinan, China.
⁶ Stem Cell Research Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁷ Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁸ Department of Pediatric Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁹ Scientific Research Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Abstract

Background: Patients with Prader-Willi syndrome (PWS) have a reduced life expectancy due to inflammation-related disease including cardiovascular disease and diabetes. Abnormal activation of peripheral immune system is postulated as a contributor. However, detailed features of the peripheral immune cells in PWS have not been fully elucidated.

Methods: Serum inflammatory cytokines were measured in healthy controls (n=13) and PWS patients (n=10) using a 65- multiplex cytokine assays. Changes of the peripheral immune cells in PWS was assessed by single-cell RNA sequencing (scRNA-seq) and high-dimensional mass cytometry (CyTOF) using peripheral blood mononuclear cells (PBMCs) from PWS patients (n=6) and healthy controls (n=12).

Results: PWS patients exhibited hyper-inflammatory signatures in PBMCs and monocytes were the most pronounced. Most inflammatory serum cytokines were increased in PWS, including IL-1β, IL-2R, IL-12p70, and TNF-α. The characteristics of monocytes evaluated by scRNA-seq and CyTOF showed that CD16⁺ monocytes were significantly increased in PWS patients. Functional pathway analysis revealed that CD16⁺ monocytes upregulated pathways in PWS were closely associated with TNF/IL-1β- driven inflammation signaling. The CellChat analysis identified CD16⁺ monocytes transmitted chemokine and cytokine signaling to drive inflammatory process in other cell types. Finally, we explored the PWS deletion region 15q11-q13 might be responsible for elevated levels of inflammation in the peripheral immune system.

Conclusion: The study highlights that CD16⁺ monocytes contributor to the hyper-inflammatory state of PWS which provides potential targets for immunotherapy in the future and expands our knowledge of peripheral immune cells in PWS at the single cell level for the first time.

Keywords: CD16+monocytes; Prader-Willi Syndrome; inflammation; mass cytometry; single-cell RNA sequencing.

Publication types

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

MeSH terms

Cytokines / genetics
Humans
Inflammation / complications
Leukocytes, Mononuclear / metabolism
Monocytes / metabolism
Prader-Willi Syndrome* / complications
Prader-Willi Syndrome* / genetics
Prader-Willi Syndrome* / metabolism
Transcriptome

Substances

Cytokines

Grants and funding

This work was supported by grants from the National Natural Science Foundation (No. 81974124), special funds for Taishan Scholar Project (No. tsqn20161071) and China Association for Science and Technology (No. 2022YJKT09).