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

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; Bruce D. Levy

iScience (Oct 2022)

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

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,
Bruce D. Levy

Affiliations

Thayse R. Brüggemann: 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

Journal volume & issue: Vol. 25, no. 10
p. 105185

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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