S1PR4‐dependent CCL2 production promotes macrophage recruitment in a murine psoriasis model

  • The sphingolipid sphingosine‐1‐phosphate (S1P) fulfills distinct functions in immune cell biology via binding to five G protein‐coupled receptors. The immune cell‐specific sphingosine‐1‐phosphate receptor 4 (S1pr4) was connected to the generation of IL‐17‐producing T cells through regulation of cytokine production in innate immune cells. Therefore, we explored whether S1pr4 affected imiquimod‐induced murine psoriasis via regulation of IL‐17 production. We did not observe altered IL‐17 production, although psoriasis severity was reduced in S1pr4‐deficient mice. Instead, ablation of S1pr4 attenuated the production of CCL2, IL‐6, and CXCL1 and subsequently reduced the number of infiltrating monocytes and granulocytes. A connection between S1pr4, CCL2, and Mϕ infiltration was also observed in Zymosan‐A induced peritonitis. Boyden chamber migration assays functionally linked reduced CCL2 production in murine skin and attenuated monocyte migration when S1pr4 was lacking. Mechanistically, S1pr4 signaling synergized with TLR signaling in resident Mϕs to produce CCL2, likely via the NF‐κB pathway. We propose that S1pr4 activation enhances TLR response of resident Mϕs to increase CCL2 production, which attracts further Mϕs. Thus, S1pr4 may be a target to reduce perpetuating inflammatory responses.

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Author:Christian Schuster, Arnaud HuardORCiDGND, Evelyn Nicole Joy Sirait-FischerORCiDGND, Christina Dillmann, Bernhard BrüneORCiD, Andreas WeigertORCiDGND
Parent Title (English):European journal of immunology
Publisher:WILEY-VCH Verlag GmbH & Co. KGaA
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2020/02/04
Date of first Publication:2020/02/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/10/27
Tag:Mφs; S1PR4; psoriasis
Page Number:7
First Page:839
Last Page:845
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0