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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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.
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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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