1. Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization
- Author
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Thayse R. Brüggemann, Troy Carlo, Nandini Krishnamoorthy, Melody G. Duvall, Raja-Elie E. Abdulnour, Julie Nijmeh, Hong Yong Peh, Harilaos Filippakis, Roxanne H. Croze, Byoungsook Goh, Sungwhan F. Oh, and Bruce D. Levy more...
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Immune response ,cell biology ,Science - Abstract
Summary: Lipid phosphate phosphatases are a family of enzymes with diverse cellular metabolic functions. Phospholipid phosphatase 6 (PLPP6) is a regulator of cellular polyisoprenyl phosphates; however, its in vivo functions remain to be determined. Here, mouse PLPP6 was characterized to possess similar catalytic properties as the human enzyme. Plpp6 knockout mice (Plpp6−/−) were generated and displayed decreased airway allergen sensitization, pointing to a role for PLPP6 in the early events of lung allergic responses. Dendritic cell (DC) responses were investigated and endocytosis of allergen via macropinocytosis was decreased in Plpp6−/− DCs that had lower cholesterol content. When reversed by cholesterol loading, the DC macropinocytosis defect is corrected. Adoptive transfer of Plpp6−/− DCs to wild-type mice during sensitization was sufficient to decrease allergen-induced responses. Together, our findings have identified PLPP6 as a pivotal regulator of DC cholesterol content and macropinocytosis, cellular mechanisms that are important for pathologic responses in allergen-induced lung inflammation. more...
- Published
- 2022
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