TY  - JOUR
A1  - Syed, Shahzad Nawaz
A1  - Raue, Rebecca
A1  - Weigert, Andreas
A1  - Knethen, Andreas von
A1  - Brüne, Bernhard
T1  - Macrophage S1PR1 signaling alters angiogenesis and lymphangiogenesis during skin inflammation
T2  - Cells
N2  - 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.
KW  - macrophage
KW  - S1PR1
KW  - sphingosine-1-phosphate
KW  - psoriasis
KW  - inflammation
KW  - lymphangiogenesis
KW  - angiogenesis
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50868
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-508687
SN  - 2073-4409
N1  - 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
VL  - 8
IS  - 8, Art. 785
SP  - 1
EP  - 19
PB  - MDPI
CY  - Basel
ER  -