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Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization
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 catal...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550614/ https://www.ncbi.nlm.nih.gov/pubmed/36238896 http://dx.doi.org/10.1016/j.isci.2022.105185 |
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author | 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. |
author_facet | 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. |
author_sort | Brüggemann, Thayse R. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9550614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-95506142022-10-12 Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization 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. iScience Article 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. Elsevier 2022-09-23 /pmc/articles/PMC9550614/ /pubmed/36238896 http://dx.doi.org/10.1016/j.isci.2022.105185 Text en © 2022. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article 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. Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization |
title | Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization |
title_full | Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization |
title_fullStr | Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization |
title_full_unstemmed | Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization |
title_short | Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization |
title_sort | mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9550614/ https://www.ncbi.nlm.nih.gov/pubmed/36238896 http://dx.doi.org/10.1016/j.isci.2022.105185 |
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