Open AccessLPA suppresses T cell function by altering the cytoskeleton and disrupting immune synapse formation
Author(s) -
Kimberly N. Kremer,
Alan Buser,
Dean Thumkeo,
Shuh Narumiya,
Jordan Jacobelli,
Roberta Pelanda,
Raul M. Torres
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2118816119
Subject(s) - immunological synapse , microbiology and biotechnology , t cell , biology , t cell receptor , cytotoxic t cell , immune system , actin , lysophosphatidic acid , cytoskeleton , rhoa , receptor , cell , signal transduction , immunology , biochemistry , in vitro
Significance Cancers and chronic infectious pathogens often evade immune-mediated elimination by suppressing T cell function via engaging inhibitory receptors expressed on T cells. The phospholipid lysophosphatidic acid (LPA) is often increased systemically from basal concentrations upon development of cancer and chronic infections. We previously showed that, at these elevated concentrations, LPA suppresses the ability of CD8 T cells to kill malignant cells and to control tumor growth. Here, we demonstrate that LPA signaling suppresses T cell function via disrupting T cell receptor–induced cytoskeletal dynamics, immune synapse formation, signal transduction, and the tubulin code. This report identifies a targetable mechanism of receptor-mediated inhibition of T cell function that could be used in combination therapies to enhance antitumor and antiviral immunity.