Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations
Background and aimAlkaline sphingomyelinase (NPP7) is expressed by intestinal epithelial cells and is crucial for the digestion of dietary sphingomyelin. NPP7 also inactivates proinflammatory mediators including platelet-activating factor and lysophosphatidylcholine. The aim of this study was to exa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1050625/full |
| _version_ | 1797947239068336128 |
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| author | Manar Alyamani Manar Alyamani Mohammad Kadivar Mohammad Kadivar Jonas Erjefält Bengt Johansson-Lindbom Rui-Dong Duan Åke Nilsson Åke Nilsson Jan Marsal Jan Marsal Jan Marsal |
| author_facet | Manar Alyamani Manar Alyamani Mohammad Kadivar Mohammad Kadivar Jonas Erjefält Bengt Johansson-Lindbom Rui-Dong Duan Åke Nilsson Åke Nilsson Jan Marsal Jan Marsal Jan Marsal |
| author_sort | Manar Alyamani |
| collection | DOAJ |
| description | Background and aimAlkaline sphingomyelinase (NPP7) is expressed by intestinal epithelial cells and is crucial for the digestion of dietary sphingomyelin. NPP7 also inactivates proinflammatory mediators including platelet-activating factor and lysophosphatidylcholine. The aim of this study was to examine a potential role for NPP7 in the homeostasis of the intestinal immune system.MethodsWe quantified the numbers of B-lymphocytes, plasma cells, T-lymphocytes including regulatory T-lymphocytes (Tregs), natural killer cells, dendritic cells, macrophages, and neutrophils, in the small and large intestines, the mesenteric lymph nodes and the spleens of heterozygous and homozygous NPP7 knockout (KO) and wildtype (WT) mice. Tissues were examined by immunohistochemistry and stainings quantified using computerized image analysis.ResultsThe numbers of both small and large intestinal CD3ε+, CD4+, and CD8α+ T-lymphocytes were significantly higher in NPP7 KO compared to WT mice (with a dose-response relationship in the large intestine), whereas Treg numbers were unchanged, and dendritic cell numbers reduced. In contrast, the numbers of CD3ε+ and CD4+ T-lymphocytes in mesenteric lymph nodes were significantly reduced in NPP7 KO mice, while no differences were observed in spleens. The numbers of B-lymphocytes, plasma cells, natural killer cells, macrophages, and neutrophils were similar between genotypes.ConclusionNPP7 contributes to the regulation of dendritic cell and T-lymphocyte numbers in mesenteric lymph nodes and both the small and large intestines, thus playing a role in the homeostasis of gut immunity. Although it is likely that the downstream effects of NPP7 activity involve the sphingomyelin metabolites ceramide and spingosine-1-phosphate, the exact mechanisms behind this regulatory function of NPP7 need to be addressed in future studies. |
| first_indexed | 2024-04-10T21:24:37Z |
| format | Article |
| id | doaj.art-12a3a615924140229854901bf23998d7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T21:24:37Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-12a3a615924140229854901bf23998d72023-01-20T00:42:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10506251050625Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populationsManar Alyamani0Manar Alyamani1Mohammad Kadivar2Mohammad Kadivar3Jonas Erjefält4Bengt Johansson-Lindbom5Rui-Dong Duan6Åke Nilsson7Åke Nilsson8Jan Marsal9Jan Marsal10Jan Marsal11Immunology Section, Department of Experimental Medical Science, Lund University, Lund, SwedenUnit of Airway Inflammation, Department of Experimental Medical Science, Lund University, Lund, SwedenImmunology Section, Department of Experimental Medical Science, Lund University, Lund, SwedenDepartment of Health Technology, Technical University of Denmark, Lyngby, DenmarkUnit of Airway Inflammation, Department of Experimental Medical Science, Lund University, Lund, SwedenImmunology Section, Department of Experimental Medical Science, Lund University, Lund, SwedenSection of Medicine, Department of Clinical Sciences, Lund University, Lund, SwedenSection of Medicine, Department of Clinical Sciences, Lund University, Lund, SwedenDepartment of Gastroenterology, Skane University Hospital, Lund/Malmö, SwedenImmunology Section, Department of Experimental Medical Science, Lund University, Lund, SwedenSection of Medicine, Department of Clinical Sciences, Lund University, Lund, SwedenDepartment of Gastroenterology, Skane University Hospital, Lund/Malmö, SwedenBackground and aimAlkaline sphingomyelinase (NPP7) is expressed by intestinal epithelial cells and is crucial for the digestion of dietary sphingomyelin. NPP7 also inactivates proinflammatory mediators including platelet-activating factor and lysophosphatidylcholine. The aim of this study was to examine a potential role for NPP7 in the homeostasis of the intestinal immune system.MethodsWe quantified the numbers of B-lymphocytes, plasma cells, T-lymphocytes including regulatory T-lymphocytes (Tregs), natural killer cells, dendritic cells, macrophages, and neutrophils, in the small and large intestines, the mesenteric lymph nodes and the spleens of heterozygous and homozygous NPP7 knockout (KO) and wildtype (WT) mice. Tissues were examined by immunohistochemistry and stainings quantified using computerized image analysis.ResultsThe numbers of both small and large intestinal CD3ε+, CD4+, and CD8α+ T-lymphocytes were significantly higher in NPP7 KO compared to WT mice (with a dose-response relationship in the large intestine), whereas Treg numbers were unchanged, and dendritic cell numbers reduced. In contrast, the numbers of CD3ε+ and CD4+ T-lymphocytes in mesenteric lymph nodes were significantly reduced in NPP7 KO mice, while no differences were observed in spleens. The numbers of B-lymphocytes, plasma cells, natural killer cells, macrophages, and neutrophils were similar between genotypes.ConclusionNPP7 contributes to the regulation of dendritic cell and T-lymphocyte numbers in mesenteric lymph nodes and both the small and large intestines, thus playing a role in the homeostasis of gut immunity. Although it is likely that the downstream effects of NPP7 activity involve the sphingomyelin metabolites ceramide and spingosine-1-phosphate, the exact mechanisms behind this regulatory function of NPP7 need to be addressed in future studies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1050625/fullalkaline sphingomyelinaseNPP7inflammatory bowel diseaseintestineknockoutS1P |
| spellingShingle | Manar Alyamani Manar Alyamani Mohammad Kadivar Mohammad Kadivar Jonas Erjefält Bengt Johansson-Lindbom Rui-Dong Duan Åke Nilsson Åke Nilsson Jan Marsal Jan Marsal Jan Marsal Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations Frontiers in Immunology alkaline sphingomyelinase NPP7 inflammatory bowel disease intestine knockout S1P |
| title | Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations |
| title_full | Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations |
| title_fullStr | Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations |
| title_full_unstemmed | Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations |
| title_short | Alkaline sphingomyelinase (NPP7) impacts the homeostasis of intestinal T lymphocyte populations |
| title_sort | alkaline sphingomyelinase npp7 impacts the homeostasis of intestinal t lymphocyte populations |
| topic | alkaline sphingomyelinase NPP7 inflammatory bowel disease intestine knockout S1P |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1050625/full |
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