S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling
Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentratio...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/7685142 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841524619976114176 |
|---|---|
| author | Ashok Kumar Jesus Zamora-Pineda Emilie Degagné Julie D. Saba |
| author_facet | Ashok Kumar Jesus Zamora-Pineda Emilie Degagné Julie D. Saba |
| author_sort | Ashok Kumar |
| collection | DOAJ |
| description | Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC). Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes. |
| format | Article |
| id | doaj-art-518d3a06f35342ba8fbcbe47f3b61f87 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-518d3a06f35342ba8fbcbe47f3b61f872025-02-03T05:47:45ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/76851427685142S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory SignalingAshok Kumar0Jesus Zamora-Pineda1Emilie Degagné2Julie D. Saba3Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Madhya Pradesh 462020, IndiaChildren’s Hospital Oakland Research Institute and UCSF Benioff Children’s Hospital Oakland, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USAChildren’s Hospital Oakland Research Institute and UCSF Benioff Children’s Hospital Oakland, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USAChildren’s Hospital Oakland Research Institute and UCSF Benioff Children’s Hospital Oakland, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USASphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC). Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human SGPL1, the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes.http://dx.doi.org/10.1155/2017/7685142 |
| spellingShingle | Ashok Kumar Jesus Zamora-Pineda Emilie Degagné Julie D. Saba S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling Mediators of Inflammation |
| title | S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling |
| title_full | S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling |
| title_fullStr | S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling |
| title_full_unstemmed | S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling |
| title_short | S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling |
| title_sort | s1p lyase regulation of thymic egress and oncogenic inflammatory signaling |
| url | http://dx.doi.org/10.1155/2017/7685142 |
| work_keys_str_mv | AT ashokkumar s1plyaseregulationofthymicegressandoncogenicinflammatorysignaling AT jesuszamorapineda s1plyaseregulationofthymicegressandoncogenicinflammatorysignaling AT emiliedegagne s1plyaseregulationofthymicegressandoncogenicinflammatorysignaling AT juliedsaba s1plyaseregulationofthymicegressandoncogenicinflammatorysignaling |