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 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.

Download full text files

Export metadata

Author:Shahzad Nawaz SyedORCiDGND, Rebecca Raue, Andreas WeigertORCiDGND, Andreas von KnethenORCiDGND, Bernhard BrüneORCiD
Pubmed Id:
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/07/28
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/09/02
Tag:S1PR1; angiogenesis; inflammation; lymphangiogenesis; macrophage; psoriasis; sphingosine-1-phosphate
Issue:8, Art. 785
Page Number:19
First Page:1
Last Page:19
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Institutes:Medizin / Medizin
Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0