Elevated Expression and Activation of GPR15 in Immune Cells in Graves' Disease

Jing Zhao; Xuerong Liu; Jianbin Xu; Yudie Fang; Peng Du; Chaoqun Gao; Tiantian Cai; Zhaohua Gu; Qiu Qin; Jin'an Zhang

doi:10.3390/biom12121899

Elevated Expression and Activation of GPR15 in Immune Cells in Graves' Disease

Biomolecules. 2022 Dec 18;12(12):1899. doi: 10.3390/biom12121899.

Authors

Jing Zhao^{1

2}, Xuerong Liu¹, Jianbin Xu¹, Yudie Fang¹, Peng Du¹, Chaoqun Gao¹, Tiantian Cai¹, Zhaohua Gu³, Qiu Qin¹, Jin'an Zhang¹

Affiliations

¹ Department of Endocrinology and Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201508, China.
² Department of Endocrinology, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi 214000, China.
³ Zhoupu Community Health Service Center of Pudong New Area, Shanghai 201508, China.

Abstract

GPR15 plays an important role in lymphocyte homing and is a key immune molecule to maintain organ immune homeostasis. Yet, no study on the association between GPR15 and Graves' disease (GD) is available. In this study, we systematically investigated the expression of GPR15 in different types of immune cells and different tissues of GD patients. We found that the expressions of GPR15 and GPR15L in peripheral blood of GD patients were increased compared with those in healthy controls. A flow cytometry analysis showed that GPR15 positive cells were mainly CD14+ monocytes and CD56+ natural killer cells (NK cells) of innate immunity, T helper cells and cytotoxic T cells of adaptive immunity. We also found that the expressions of GPR15 and GPR15L in the PBMC of GD patients were positively correlated with the Tfh-specific cytokines IL21 and IL4. In addition, immunohistochemistry showed that the level of GPR15 in thyroid tissue of GD patients was higher than that of the control group. Our results demonstrate for the first time that GPR15 is highly expressed in various immune cells in GD patients, suggesting that GPR15-GPR15L is associated with the activation and infiltration of proinflammatory immune cells in the thyroid tissue of GD patients.

Keywords: GPR15; GPR15L; Graves’ disease; IL21; IL4; Tfh.

Publication types

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

MeSH terms

Graves Disease* / metabolism
Humans
Killer Cells, Natural
Leukocytes, Mononuclear* / metabolism
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism
Receptors, Peptide
T-Lymphocytes, Helper-Inducer

Substances

GPR15 protein, human
Receptors, Peptide
Receptors, G-Protein-Coupled

Grants and funding

This research was funded by: The National Natural Science Foundation of China (Grant No. 81900710 and 81873636), Shanghai Pudong New Area second round of medical discipline construction project-clinical characteristic discipline (PWYts2021-09), Clinical Research Center of thyroid diseases of Shanghai Health Medical College (20MC20200002), “Top-100 Talent Cultivation Plan” of Shanghai University of Medicine and Health Sciences (No. A3-0200-21-311007).