Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Troy Carlo
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Nandini Krishnamoorthy
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Melody G. Duvall
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Raja-Elie E. Abdulnour
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Julie Nijmeh
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Hong Yong Peh
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Harilaos Filippakis
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Roxanne H. Croze
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Byoungsook Goh
Center for Experimental Therapeutics and Reperfusion Injury, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Sungwhan F. Oh
Center for Experimental Therapeutics and Reperfusion Injury, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Bruce D. Levy
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; Corresponding author
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.
