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

Xue Chen (), Yanyan Xu, Qidi Chen, Heng Zhang, Yu Zeng, Yan Geng, Lei Shen, Fubin Li, Lei Chen, Guo-Qiang Chen, Chuanxin Huang () and Junling Liu ()
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Xue Chen: Shanghai University
Yanyan Xu: Shanghai Jiao Tong University School of Medicine
Qidi Chen: Shanghai Jiao Tong University School of Medicine
Heng Zhang: Shanghai Jiao Tong University School of Medicine
Yu Zeng: Shanghai Jiao Tong University School of Medicine
Yan Geng: Shanghai Jiao Tong University School of Medicine
Lei Shen: Shanghai Jiao Tong University School of Medicine
Fubin Li: Shanghai Jiao Tong University School of Medicine
Lei Chen: Shanghai Jiao Tong University School of Medicine
Guo-Qiang Chen: Shanghai Jiao Tong University School of Medicine
Chuanxin Huang: Shanghai Jiao Tong University School of Medicine
Junling Liu: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30444-y

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