Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation
The bioactive lipid sphingosine-1-phosphate (S1P), along with its receptors, modulates lymphocyte trafficking and immune responses to regulate skin inflammation. Macrophages are important in the pathogenesis of psoriasiform skin inflammation and express various S1P receptors. How they respond to S1P...
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MDPI AG
2019-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/785 |
| _version_ | 1827838974682464256 |
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| author | Shahzad Nawaz Syed Rebecca Raue Andreas Weigert Andreas von Knethen Bernhard Brüne |
| author_facet | Shahzad Nawaz Syed Rebecca Raue Andreas Weigert Andreas von Knethen Bernhard Brüne |
| author_sort | Shahzad Nawaz Syed |
| collection | DOAJ |
| description | The bioactive lipid sphingosine-1-phosphate (S1P), along with its receptors, modulates lymphocyte trafficking and immune responses to regulate skin inflammation. Macrophages are important in the pathogenesis of psoriasiform skin inflammation and express various S1P receptors. How they respond to S1P in skin inflammation remains unknown. We show that myeloid specific S1P receptor 1 (S1PR1) deletion enhances early inflammation in a mouse model of imiquimod-induced psoriasis, without altering the immune cell infiltrate. Mechanistically, myeloid S1PR1 deletion altered the formation of IL-1β, VEGF-A, and VEGF-C, and their receptors’ expression in psoriatic skin, which subsequently lead to reciprocal regulation of neoangiogenesis and neolymphangiogenesis. Experimental findings were corroborated in human clinical datasets and in knockout macrophages in vitro. Increased blood vessel but reduced lymph vessel density may explain the exacerbated inflammatory phenotype in conditional knockout mice. These findings assign a novel role to macrophage S1PR1 and provide a rationale for therapeutically targeting local S1P during skin inflammation. |
| first_indexed | 2024-03-12T07:14:44Z |
| format | Article |
| id | doaj.art-e3c7d39f5161462ea6a37d3343105291 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:14:44Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e3c7d39f5161462ea6a37d33431052912023-09-02T22:54:39ZengMDPI AGCells2073-44092019-07-018878510.3390/cells8080785cells8080785Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin InflammationShahzad Nawaz Syed0Rebecca Raue1Andreas Weigert2Andreas von Knethen3Bernhard Brüne4Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyThe bioactive lipid sphingosine-1-phosphate (S1P), along with its receptors, modulates lymphocyte trafficking and immune responses to regulate skin inflammation. Macrophages are important in the pathogenesis of psoriasiform skin inflammation and express various S1P receptors. How they respond to S1P in skin inflammation remains unknown. We show that myeloid specific S1P receptor 1 (S1PR1) deletion enhances early inflammation in a mouse model of imiquimod-induced psoriasis, without altering the immune cell infiltrate. Mechanistically, myeloid S1PR1 deletion altered the formation of IL-1β, VEGF-A, and VEGF-C, and their receptors’ expression in psoriatic skin, which subsequently lead to reciprocal regulation of neoangiogenesis and neolymphangiogenesis. Experimental findings were corroborated in human clinical datasets and in knockout macrophages in vitro. Increased blood vessel but reduced lymph vessel density may explain the exacerbated inflammatory phenotype in conditional knockout mice. These findings assign a novel role to macrophage S1PR1 and provide a rationale for therapeutically targeting local S1P during skin inflammation.https://www.mdpi.com/2073-4409/8/8/785macrophageS1PR1sphingosine-1-phosphatepsoriasisinflammationlymphangiogenesisangiogenesis |
| spellingShingle | Shahzad Nawaz Syed Rebecca Raue Andreas Weigert Andreas von Knethen Bernhard Brüne Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation Cells macrophage S1PR1 sphingosine-1-phosphate psoriasis inflammation lymphangiogenesis angiogenesis |
| title | Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation |
| title_full | Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation |
| title_fullStr | Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation |
| title_full_unstemmed | Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation |
| title_short | Macrophage S1PR1 Signaling Alters Angiogenesis and Lymphangiogenesis During Skin Inflammation |
| title_sort | macrophage s1pr1 signaling alters angiogenesis and lymphangiogenesis during skin inflammation |
| topic | macrophage S1PR1 sphingosine-1-phosphate psoriasis inflammation lymphangiogenesis angiogenesis |
| url | https://www.mdpi.com/2073-4409/8/8/785 |
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