Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization

• Published in: iScience Vol. 25; no. 10; p. 105185
• Main Authors: Brüggemann, Thayse R., Carlo, Troy, Krishnamoorthy, Nandini, Duvall, Melody G., Abdulnour, Raja-Elie E., Nijmeh, Julie, Peh, Hong Yong, Filippakis, Harilaos, Croze, Roxanne H., Goh, Byoungsook, Oh, Sungwhan F., Levy, Bruce D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.10.2022; Elsevier
• Subjects: cell biology; Immune response; Immune response; cell biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105185

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. [Display omitted] •Mouse Plpp6 converts presqualene diphosphate into presqualene monophosphate•Mouse Plpp6 is regulated during allergic lung inflammation•Plpp6−/− DCs have lower cholesterol content and decreased allergen macropinocytosis•Plpp6−/− mice have decreased allergic lung inflammation in response to HDM Immune response; Cell biology.