2. Academic Validation
  3. The phosphatase PTEN links platelets with immune regulatory functions of mouse T follicular helper cells

The phosphatase PTEN links platelets with immune regulatory functions of mouse T follicular helper cells

  • Nat Commun. 2022 May 19;13(1):2762. doi: 10.1038/s41467-022-30444-y.
Xue Chen 1,  Yanyan Xu 2,  Qidi Chen 2,  Heng Zhang 3,  Yu Zeng 3,  Yan Geng 2,  Lei Shen 3,  Fubin Li 3,  Lei Chen 3,  Guo-Qiang Chen 2,  Chuanxin Huang 4,  Junling Liu 5
Affiliations

Affiliations

  • 1 School of Life Sciences, Shanghai University, 333 Nanchen Road, Shanghai, 200444, China. chenxue-snow@163.com.
  • 2 Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
  • 3 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
  • 4 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. huangcx@shsmu.edu.cn.
  • 5 Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. liujl@shsmu.edu.cn.
PMID: 35589797 DOI: 10.1038/s41467-022-30444-y
Abstract

Beyond a function in hemostasis and thrombosis, platelets can regulate innate and adaptive immune responses. Hyperactive platelets are frequently associated with multiple human autoimmune diseases, yet their pathogenic functions in these diseases have not been fully established. Emerging studies show an essential function of the Phosphatase and tensin homolog (PTEN) in maintenance of immune homeostasis. Here, we show that mice with platelet-specific deletion of PTEN, develop age-related lymphoproliferative diseases and humoral autoimmunity not seen in wildtype Animals. Platelet-specific Pten-deficient mice have aberrant T cell activation, excessive T follicular helper (Tfh) cell responses and accumulation of platelet aggregates in lymph nodes. Transferred Pten-deficient platelets are able to infiltrate into the peripheral lymphoid tissues and form more aggregates. Moreover, Pten-deficient platelets are hyperactive and overproduce multiple Tfh-promoting cytokines via activation of the PDK1/mTORC2-AKT-SNAP23 pathway. Pten-deficient platelets show enhanced interaction with CD4+ T cells and promote conversion of CD4+ T cells into Tfh cells. Our results implicate PTEN in platelet-mediated immune homeostasis, and provide evidence that hyperactive platelets function as an important mediator in autoimmune diseases using mouse models.

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