Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress
T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)-mediated metab...
Gespeichert in:
| Veröffentlicht in: | The Journal of experimental medicine 2016-11, Vol.213 (12), p.2773-2791 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2791 |
|---|---|
| container_issue | 12 |
| container_start_page | 2773 |
| container_title | The Journal of experimental medicine |
| container_volume | 213 |
| creator | Zamora-Pineda, Jesus Kumar, Ashok Suh, Jung H Zhang, Meng Saba, Julie D |
| description | T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)-mediated metabolism. Although SPL is robustly expressed in thymic epithelial cells (TECs), in this study, we show that deleting SPL in CD11c
dendritic cells (DCs), rather than TECs or other stromal cells, disrupts the S1P gradient, preventing egress. Adoptive transfer of peripheral wild-type DCs rescued the egress phenotype of DC-specific SPL knockout mice. These studies identify DCs as metabolic gatekeepers of thymic egress. Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeostatic regulation of thymic export. |
| doi_str_mv | 10.1084/jem.20160287 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5110016</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1836733167</sourcerecordid><originalsourceid>FETCH-LOGICAL-c417t-b320c10f05f7cf0a04ae52f6d5c8f3bd3d050afb4304ef0a5ddbe91deb3a181a3</originalsourceid><addsrcrecordid>eNqNUU1PwzAMjRCIjcGNM-qRAx12k7TdBQltfEmTuMA5Slu369QvkhZp_55M-xDcuNiy_fzk58fYNcIUIRb3a6qnAWAIQRydsDFKAf5M8viUjQGCwEeAaMQurF0DoBAyPGejIIoRZgEfs8WCmsyUfZl6KVWVZ7tV2RStLRvy0e9WrWvonrxqoy15hoqhcqX1-tWmdjtUGLL2kp3lurJ0tc8T9vn89DF_9ZfvL2_zx6WfCox6P-EBpAg5yDxKc9AgNMkgDzOZxjlPMp6BBJ0ngoMgN5dZltAMM0q4xhg1n7CHHW83JDVlKTW90ZXqTFlrs1GtLtXfSVOuVNF-K4nuCxg6gts9gWm_BrK9qku71a0bagerMBahQIwg_geUhxHn6MKE3e2gqWmtNZQfL0JQW4-U80gdPHLwm98qjuCDKfwHxUmOnQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1836733167</pqid></control><display><type>article</type><title>Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Zamora-Pineda, Jesus ; Kumar, Ashok ; Suh, Jung H ; Zhang, Meng ; Saba, Julie D</creator><creatorcontrib>Zamora-Pineda, Jesus ; Kumar, Ashok ; Suh, Jung H ; Zhang, Meng ; Saba, Julie D</creatorcontrib><description>T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)-mediated metabolism. Although SPL is robustly expressed in thymic epithelial cells (TECs), in this study, we show that deleting SPL in CD11c
dendritic cells (DCs), rather than TECs or other stromal cells, disrupts the S1P gradient, preventing egress. Adoptive transfer of peripheral wild-type DCs rescued the egress phenotype of DC-specific SPL knockout mice. These studies identify DCs as metabolic gatekeepers of thymic egress. Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeostatic regulation of thymic export.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20160287</identifier><identifier>PMID: 27810923</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Adoptive Transfer ; Aldehyde-Lyases - metabolism ; Animals ; Bone Marrow - metabolism ; Dendritic Cells - cytology ; Dendritic Cells - enzymology ; Endothelial Cells - enzymology ; Epithelial Cells - enzymology ; Extracellular Space - metabolism ; Hematopoiesis ; Lysophospholipids - blood ; Macrophages - cytology ; Mice, Inbred C57BL ; Monocytes - cytology ; Phenotype ; Receptors, Lysosphingolipid - metabolism ; Sphingosine - analogs & derivatives ; Sphingosine - blood ; T-Lymphocytes - cytology ; T-Lymphocytes - metabolism ; Thymus Gland - cytology ; Thymus Gland - metabolism</subject><ispartof>The Journal of experimental medicine, 2016-11, Vol.213 (12), p.2773-2791</ispartof><rights>2016 Zamora-Pineda et al.</rights><rights>2016 Zamora-Pineda et al. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-b320c10f05f7cf0a04ae52f6d5c8f3bd3d050afb4304ef0a5ddbe91deb3a181a3</citedby><cites>FETCH-LOGICAL-c417t-b320c10f05f7cf0a04ae52f6d5c8f3bd3d050afb4304ef0a5ddbe91deb3a181a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27810923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zamora-Pineda, Jesus</creatorcontrib><creatorcontrib>Kumar, Ashok</creatorcontrib><creatorcontrib>Suh, Jung H</creatorcontrib><creatorcontrib>Zhang, Meng</creatorcontrib><creatorcontrib>Saba, Julie D</creatorcontrib><title>Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)-mediated metabolism. Although SPL is robustly expressed in thymic epithelial cells (TECs), in this study, we show that deleting SPL in CD11c
dendritic cells (DCs), rather than TECs or other stromal cells, disrupts the S1P gradient, preventing egress. Adoptive transfer of peripheral wild-type DCs rescued the egress phenotype of DC-specific SPL knockout mice. These studies identify DCs as metabolic gatekeepers of thymic egress. Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeostatic regulation of thymic export.</description><subject>Adoptive Transfer</subject><subject>Aldehyde-Lyases - metabolism</subject><subject>Animals</subject><subject>Bone Marrow - metabolism</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - enzymology</subject><subject>Endothelial Cells - enzymology</subject><subject>Epithelial Cells - enzymology</subject><subject>Extracellular Space - metabolism</subject><subject>Hematopoiesis</subject><subject>Lysophospholipids - blood</subject><subject>Macrophages - cytology</subject><subject>Mice, Inbred C57BL</subject><subject>Monocytes - cytology</subject><subject>Phenotype</subject><subject>Receptors, Lysosphingolipid - metabolism</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - blood</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Thymus Gland - cytology</subject><subject>Thymus Gland - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1PwzAMjRCIjcGNM-qRAx12k7TdBQltfEmTuMA5Slu369QvkhZp_55M-xDcuNiy_fzk58fYNcIUIRb3a6qnAWAIQRydsDFKAf5M8viUjQGCwEeAaMQurF0DoBAyPGejIIoRZgEfs8WCmsyUfZl6KVWVZ7tV2RStLRvy0e9WrWvonrxqoy15hoqhcqX1-tWmdjtUGLL2kp3lurJ0tc8T9vn89DF_9ZfvL2_zx6WfCox6P-EBpAg5yDxKc9AgNMkgDzOZxjlPMp6BBJ0ngoMgN5dZltAMM0q4xhg1n7CHHW83JDVlKTW90ZXqTFlrs1GtLtXfSVOuVNF-K4nuCxg6gts9gWm_BrK9qku71a0bagerMBahQIwg_geUhxHn6MKE3e2gqWmtNZQfL0JQW4-U80gdPHLwm98qjuCDKfwHxUmOnQ</recordid><startdate>20161114</startdate><enddate>20161114</enddate><creator>Zamora-Pineda, Jesus</creator><creator>Kumar, Ashok</creator><creator>Suh, Jung H</creator><creator>Zhang, Meng</creator><creator>Saba, Julie D</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20161114</creationdate><title>Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress</title><author>Zamora-Pineda, Jesus ; Kumar, Ashok ; Suh, Jung H ; Zhang, Meng ; Saba, Julie D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-b320c10f05f7cf0a04ae52f6d5c8f3bd3d050afb4304ef0a5ddbe91deb3a181a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adoptive Transfer</topic><topic>Aldehyde-Lyases - metabolism</topic><topic>Animals</topic><topic>Bone Marrow - metabolism</topic><topic>Dendritic Cells - cytology</topic><topic>Dendritic Cells - enzymology</topic><topic>Endothelial Cells - enzymology</topic><topic>Epithelial Cells - enzymology</topic><topic>Extracellular Space - metabolism</topic><topic>Hematopoiesis</topic><topic>Lysophospholipids - blood</topic><topic>Macrophages - cytology</topic><topic>Mice, Inbred C57BL</topic><topic>Monocytes - cytology</topic><topic>Phenotype</topic><topic>Receptors, Lysosphingolipid - metabolism</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - blood</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Thymus Gland - cytology</topic><topic>Thymus Gland - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zamora-Pineda, Jesus</creatorcontrib><creatorcontrib>Kumar, Ashok</creatorcontrib><creatorcontrib>Suh, Jung H</creatorcontrib><creatorcontrib>Zhang, Meng</creatorcontrib><creatorcontrib>Saba, Julie D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zamora-Pineda, Jesus</au><au>Kumar, Ashok</au><au>Suh, Jung H</au><au>Zhang, Meng</au><au>Saba, Julie D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2016-11-14</date><risdate>2016</risdate><volume>213</volume><issue>12</issue><spage>2773</spage><epage>2791</epage><pages>2773-2791</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)-mediated metabolism. Although SPL is robustly expressed in thymic epithelial cells (TECs), in this study, we show that deleting SPL in CD11c
dendritic cells (DCs), rather than TECs or other stromal cells, disrupts the S1P gradient, preventing egress. Adoptive transfer of peripheral wild-type DCs rescued the egress phenotype of DC-specific SPL knockout mice. These studies identify DCs as metabolic gatekeepers of thymic egress. Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeostatic regulation of thymic export.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>27810923</pmid><doi>10.1084/jem.20160287</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1007 |
| ispartof | The Journal of experimental medicine, 2016-11, Vol.213 (12), p.2773-2791 |
| issn | 0022-1007 1540-9538 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5110016 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adoptive Transfer Aldehyde-Lyases - metabolism Animals Bone Marrow - metabolism Dendritic Cells - cytology Dendritic Cells - enzymology Endothelial Cells - enzymology Epithelial Cells - enzymology Extracellular Space - metabolism Hematopoiesis Lysophospholipids - blood Macrophages - cytology Mice, Inbred C57BL Monocytes - cytology Phenotype Receptors, Lysosphingolipid - metabolism Sphingosine - analogs & derivatives Sphingosine - blood T-Lymphocytes - cytology T-Lymphocytes - metabolism Thymus Gland - cytology Thymus Gland - metabolism |
| title | Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T11%3A38%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Dendritic%20cell%20sphingosine-1-phosphate%20lyase%20regulates%20thymic%20egress&rft.jtitle=The%20Journal%20of%20experimental%20medicine&rft.au=Zamora-Pineda,%20Jesus&rft.date=2016-11-14&rft.volume=213&rft.issue=12&rft.spage=2773&rft.epage=2791&rft.pages=2773-2791&rft.issn=0022-1007&rft.eissn=1540-9538&rft_id=info:doi/10.1084/jem.20160287&rft_dat=%3Cproquest_pubme%3E1836733167%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1836733167&rft_id=info:pmid/27810923&rfr_iscdi=true |