S1PR4 is required for plasmacytoid dendritic cell differentiation
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Christina Dillmann
Abstract
The sphingolipid sphingosine-1-phosphate (S1P) has various functions in immune cell biology, regulating survival, proliferation, and, most prominently, migration. S1P couples to five G protein-coupled receptors (S1PR1–5) to transduce its effects on immune cell function. Expression of S1PR4 is restricted to immune cells. However, its impact on immune cell biology is largely elusive. In the current study, we intended to answer the question of whether S1P might affect plasmacytoid dendritic cell (pDC) migration, which dominantly express S1PR4. pDC are highly specialized cells producing large amounts of type I interferon in response to TLR7/9 ligands after viral infection or during autoimmunity. Surprisingly, we noticed a reduced abundance of pDC, particularly CD4- pDC, in all organs of S1PR4-deficient vs. wildtype mice. This effect was not caused by altered migration of mature pDC, but rather a reduced potential of pDC progenitors, especially common DC progenitors, to differentiate into pDCs. In vitro studies suggested that reduced S1PR4-deficient pDC progenitor differentiation into mature pDC might be explained by both migration and differentiation of pDC progenitors in the bone marrow. As S1PR4 also affected the differentiation of CD34+ human hematopoietic stem cells into pDC, interfering with S1PR4 might be useful to reduce pDC numbers during autoimmunity.
Acknowledgements
The authors thank Praveen Mathoor and Margarethe Mijatovic for excellent technical assistance. The authors are supported by Else Kröner-Fresenius Foundation (EKFS) Research Training Group Translational Research Innovation – Pharma (TRIP), Sander Foundation (2013.036.01), Deutsche Krebshilfe (110637), and Deutsche Forschungsgemeinschaft (DFG, SFB 1039). J.M. was supported by Deutscher Akademischer Austauschdienst (DAAD) and the University of Costa Rica.
Conflict of interest disclosure: The authors declare no financial or commercial conflict of interest.
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Supplemental Material:
The online version of this article (DOI: 10.1515/hsz-2014-0271) offers supplementary material, available to authorized users.
©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Molecular Medicine of Sphingolipids
- HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
- The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
- Sphingolipids in viral infection
- Tackling the biophysical properties of sphingolipids to decipher their biological roles
- Ceramide and sphingosine in pulmonary infections
- Molecular mechanisms of erythrocyte aging
- Sphingolipids in liver injury, repair and regeneration
- Ultrasound-stimulated microbubble enhancement of radiation response
- Innate immune responses in the brain of sphingolipid lysosomal storage diseases
- Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
- The role of sphingolipids in endothelial barrier function
- The effect of altered sphingolipid acyl chain length on various disease models
- Secretory sphingomyelinase in health and disease
- Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
- Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
- The molecular medicine of acid ceramidase
- Caenorhabditis elegans as a model to study sphingolipid signaling
- S1PR4 is required for plasmacytoid dendritic cell differentiation
- Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
- Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
- Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
- Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
- Obituary
- The life and work of Dr. Robert Bittman (1942–2014)
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Molecular Medicine of Sphingolipids
- HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
- The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
- Sphingolipids in viral infection
- Tackling the biophysical properties of sphingolipids to decipher their biological roles
- Ceramide and sphingosine in pulmonary infections
- Molecular mechanisms of erythrocyte aging
- Sphingolipids in liver injury, repair and regeneration
- Ultrasound-stimulated microbubble enhancement of radiation response
- Innate immune responses in the brain of sphingolipid lysosomal storage diseases
- Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
- The role of sphingolipids in endothelial barrier function
- The effect of altered sphingolipid acyl chain length on various disease models
- Secretory sphingomyelinase in health and disease
- Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
- Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
- The molecular medicine of acid ceramidase
- Caenorhabditis elegans as a model to study sphingolipid signaling
- S1PR4 is required for plasmacytoid dendritic cell differentiation
- Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
- Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
- Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
- Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
- Obituary
- The life and work of Dr. Robert Bittman (1942–2014)
