RRC ID 71906
Author Hossain MS, Mawatari S, Fujino T.
Title Plasmalogen-Mediated Activation of GPCR21 Regulates Cytolytic Activity of NK Cells against the Target Cells.
Journal J Immunol
Abstract It is widely known that the immune system becomes slower to respond among elderly people, making them more susceptible to viral infection and cancer. The mechanism of aging-related immune deficiency remained mostly elusive. In this article, we report that plasmalogens (Pls), special phospholipids found to be reduced among the elderly population, critically control cytolytic activity of human NK cells, which is associated with activation of a cell surface receptor, G protein-coupled receptor 21 (GPCR21). We found the extracellular glycosylation site of GPCR21, which is conserved among the mammalian species, to be critically important for the activation of NK cells by Pls. The Pls-GPCR21 signaling cascade induces the expression of Perforin-1, a cytolytic pore-forming protein, via activation of STAT5 transcription factor. Inhibition of STAT5 abrogates GPCR21-mediated cytolytic activation of NK cells against the target cancer cells. In addition, oral ingestion of Pls inhibited cancer growth in SCID mice and inhibited the systemic spread of murine CMV in adult C57BL/6J mice. These findings advocate that Pls-GPCR21 signaling could be critical in maintaining NK cell function, and that the age-related reduction of this signaling cascade could be one of the factors behind immune deficiency in mammals, including humans.
Volume 209(2)
Pages 310-325
Published 2022-7-15
DOI 10.4049/jimmunol.2200183
PII jimmunol.2200183
PMID 35777853
MeSH Adult Aged Animals Cytotoxicity, Immunologic Humans Killer Cells, Natural* Mammals Mice Mice, Inbred C57BL Mice, SCID Perforin / metabolism Plasmalogens* / metabolism Pore Forming Cytotoxic Proteins / metabolism Receptors, G-Protein-Coupled / metabolism Receptors, Leukotriene / metabolism* Signal Transduction
IF 4.886
Human and Animal Cells SC-1(RCB1829)