2. Academic Validation
  3. PRL2 negatively regulates FcεRI mediated activation of mast cells

PRL2 negatively regulates FcεRI mediated activation of mast cells

  • Cell Death Dis. 2025 Apr 21;16(1):322. doi: 10.1038/s41419-025-07649-2.
Xin Guo # 1,  Yunxuan Lei # 1,  Yanhua Xu 2,  Xinyue Du 1,  Lin Lin 3,  Yanping Luo 1,  Yebin Xi 1,  Yinshi Guo 2,  Xiaoyin Niu 4,  Zhaojun Wang 5,  Guangjie Chen 6
Affiliations

Affiliations

  • 1 Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Department of Allergy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. niuxiaoyin@163.com.
  • 5 Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zjwang@sjtu.edu.cn.
  • 6 Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. chenguangjie@sjtu.edu.cn.
  • # Contributed equally.
PMID: 40258807 DOI: 10.1038/s41419-025-07649-2
Abstract

Mast cells play a central role in allergic reactions, acting as key effector cells that initiate and amplify the inflammatory response. In this study, we demonstrate that Phosphatase of regenerating liver 2 (PRL2) functions as a negative regulator of FcεRI-mediated mast cell activation. In PRL2-deficient myeloid cells, PRL2 conditional knockout mice developed more severe passive systemic anaphylaxis (PSA). Although PRL2 deficiency does not impact mast cell development, in the absence of PRL2 FcεRI-mediated mast cell activation is enhanced. In the presence of IgE the expression of mast cell PRL2 is downregulated, leading to modulation of the cellular response. In PRL2-deficient mast cells, the PI3K signaling pathway is upregulated, resulting in increased calcium influx. This, in turn, enhances mast cell degranulation and the production of inflammatory mediators. Moreover, hydroxychloroquine (an inhibitor of PRL2 degradation) reduces the severity of PSA in wild-type mice. Our findings suggest that PRL2 acts as a negative regulator of FcεRI-mediated mast cell activation. Therefore, therapeutic strategies aimed at enhancing PRL2 activity in mast cells may offer a promising approach for the treatment of allergic disorders.

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