| First Author | Brüggemann TR | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 10 | Pages | 105185 |
| PubMed ID | 36238896 | Mgi Jnum | J:329994 |
| Mgi Id | MGI:7355759 | Doi | 10.1016/j.isci.2022.105185 |
| Citation | Bruggemann TR, et al. (2022) Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization. iScience 25(10):105185 |
| abstractText | 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. |
