Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea
Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (P...
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| Veröffentlicht in: | The European respiratory journal 2017-10, Vol.50 (4), p.1700833-1700833 |
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| creator | Cubillos-Zapata, Carolina Avendaño-Ortiz, Jose Hernandez-Jimenez, Enrique Toledano, Victor Casas-Martin, Jose Varela-Serrano, Anibal Torres, Marta Almendros, Isaac Casitas, Raquel Fernández-Navarro, Isabel Garcia-Sanchez, Aldara Aguirre, Luis A Farre, Ramón López-Collazo, Eduardo García-Rio, Francisco |
| description | Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8
T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human
and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8
T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8
T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients. |
| doi_str_mv | 10.1183/13993003.00833-2017 |
| format | Article |
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T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human
and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8
T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8
T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.</description><identifier>ISSN: 0903-1936</identifier><identifier>EISSN: 1399-3003</identifier><identifier>DOI: 10.1183/13993003.00833-2017</identifier><identifier>PMID: 29051270</identifier><language>eng</language><publisher>England: European Respiratory Society Journals Ltd</publisher><subject>Adult ; Animal models ; Apnea ; Apoptosis ; B7-H1 Antigen - metabolism ; Cancer ; CD8 antigen ; CD8-Positive T-Lymphocytes - physiology ; Cell activation ; Cell death ; Cell proliferation ; Cytotoxicity ; Female ; Gene Expression Regulation ; Humans ; Hypoxia ; Hypoxia-inducible factors ; Lymphocytes T ; Male ; Middle Aged ; Monocytes ; Monocytes - physiology ; PD-1 protein ; PD-L1 protein ; Programmed Cell Death 1 Receptor - metabolism ; Retinoic acid ; Signal Transduction ; Sleep ; Sleep apnea ; Sleep Apnea, Obstructive - diagnosis ; Sleep Apnea, Obstructive - metabolism ; Sleep disorders ; Suppressor cells ; T cell receptors ; Transfection ; Tumors ; Up-Regulation</subject><ispartof>The European respiratory journal, 2017-10, Vol.50 (4), p.1700833-1700833</ispartof><rights>Copyright ©ERS 2017.</rights><rights>Copyright European Respiratory Society Journals Ltd. Oct 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-3c343f6d311fcee1d660685884e999e37e9aeb79daad8955997b975b82d914cb3</citedby><cites>FETCH-LOGICAL-c378t-3c343f6d311fcee1d660685884e999e37e9aeb79daad8955997b975b82d914cb3</cites><orcidid>&quot;0000-0002-2478-2700 ; &quot;0000-0003-0903-9385 ; 0000-0002-2478-2700 ; 0000-0003-0903-9385</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29051270$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cubillos-Zapata, Carolina</creatorcontrib><creatorcontrib>Avendaño-Ortiz, Jose</creatorcontrib><creatorcontrib>Hernandez-Jimenez, Enrique</creatorcontrib><creatorcontrib>Toledano, Victor</creatorcontrib><creatorcontrib>Casas-Martin, Jose</creatorcontrib><creatorcontrib>Varela-Serrano, Anibal</creatorcontrib><creatorcontrib>Torres, Marta</creatorcontrib><creatorcontrib>Almendros, Isaac</creatorcontrib><creatorcontrib>Casitas, Raquel</creatorcontrib><creatorcontrib>Fernández-Navarro, Isabel</creatorcontrib><creatorcontrib>Garcia-Sanchez, Aldara</creatorcontrib><creatorcontrib>Aguirre, Luis A</creatorcontrib><creatorcontrib>Farre, Ramón</creatorcontrib><creatorcontrib>López-Collazo, Eduardo</creatorcontrib><creatorcontrib>García-Rio, Francisco</creatorcontrib><title>Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea</title><title>The European respiratory journal</title><addtitle>Eur Respir J</addtitle><description>Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8
T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human
and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8
T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8
T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.</description><subject>Adult</subject><subject>Animal models</subject><subject>Apnea</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Cancer</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - physiology</subject><subject>Cell activation</subject><subject>Cell death</subject><subject>Cell proliferation</subject><subject>Cytotoxicity</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-inducible factors</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monocytes</subject><subject>Monocytes - physiology</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Programmed Cell Death 1 Receptor - metabolism</subject><subject>Retinoic acid</subject><subject>Signal Transduction</subject><subject>Sleep</subject><subject>Sleep apnea</subject><subject>Sleep Apnea, Obstructive - diagnosis</subject><subject>Sleep Apnea, Obstructive - metabolism</subject><subject>Sleep disorders</subject><subject>Suppressor cells</subject><subject>T cell receptors</subject><subject>Transfection</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0903-1936</issn><issn>1399-3003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1Lw0AQhhdRbK3-AkECXrxsO5NJsrtHqR8VAnqo57BJNrA1X2YbsP_epB8evMzA8LzDzMPYLcIcUdICSSkCoDmAJOI-oDhj03HKx_E5m4IC4qgomrAr5zYAGAWEl2ziKwjRFzBl8WrXNj9Wc1vnfWZy7-OJx7gYKnpZ1zi31eWXZ6tW2855a56ZsvSKvs62tqk9W3uuNKb1dFs3Rl-zi0KXztwc-4x9vjyvlysev7--LR9jnpGQW04ZBVREOSEWmTGYRxFEMpQyMEopQ8IobVKhcq1zqcJQKZEqEabSzxUGWUoz9nDY23bNd2_cNqmsGy_TtWl6l6AKA4giKWhA7_-hm6bv6uG6gZIBSBA-DBQdqP3LnSmStrOV7nYJQjLKTk6yk73sZJQ9pO6Ou_u0Mvlf5mSXfgGZ13cM</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Cubillos-Zapata, Carolina</creator><creator>Avendaño-Ortiz, Jose</creator><creator>Hernandez-Jimenez, Enrique</creator><creator>Toledano, Victor</creator><creator>Casas-Martin, Jose</creator><creator>Varela-Serrano, Anibal</creator><creator>Torres, Marta</creator><creator>Almendros, Isaac</creator><creator>Casitas, Raquel</creator><creator>Fernández-Navarro, Isabel</creator><creator>Garcia-Sanchez, Aldara</creator><creator>Aguirre, Luis A</creator><creator>Farre, Ramón</creator><creator>López-Collazo, Eduardo</creator><creator>García-Rio, Francisco</creator><general>European Respiratory Society Journals Ltd</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>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/&quot;0000-0002-2478-2700</orcidid><orcidid>https://orcid.org/&quot;0000-0003-0903-9385</orcidid><orcidid>https://orcid.org/0000-0002-2478-2700</orcidid><orcidid>https://orcid.org/0000-0003-0903-9385</orcidid></search><sort><creationdate>201710</creationdate><title>Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea</title><author>Cubillos-Zapata, Carolina ; Avendaño-Ortiz, Jose ; Hernandez-Jimenez, Enrique ; Toledano, Victor ; Casas-Martin, Jose ; Varela-Serrano, Anibal ; Torres, Marta ; Almendros, Isaac ; Casitas, Raquel ; Fernández-Navarro, Isabel ; Garcia-Sanchez, Aldara ; Aguirre, Luis A ; Farre, Ramón ; López-Collazo, Eduardo ; García-Rio, Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-3c343f6d311fcee1d660685884e999e37e9aeb79daad8955997b975b82d914cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Animal models</topic><topic>Apnea</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Cancer</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - physiology</topic><topic>Cell activation</topic><topic>Cell death</topic><topic>Cell proliferation</topic><topic>Cytotoxicity</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia-inducible factors</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monocytes</topic><topic>Monocytes - physiology</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Programmed Cell Death 1 Receptor - metabolism</topic><topic>Retinoic acid</topic><topic>Signal Transduction</topic><topic>Sleep</topic><topic>Sleep apnea</topic><topic>Sleep Apnea, Obstructive - diagnosis</topic><topic>Sleep Apnea, Obstructive - metabolism</topic><topic>Sleep disorders</topic><topic>Suppressor cells</topic><topic>T cell receptors</topic><topic>Transfection</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cubillos-Zapata, Carolina</creatorcontrib><creatorcontrib>Avendaño-Ortiz, Jose</creatorcontrib><creatorcontrib>Hernandez-Jimenez, Enrique</creatorcontrib><creatorcontrib>Toledano, Victor</creatorcontrib><creatorcontrib>Casas-Martin, Jose</creatorcontrib><creatorcontrib>Varela-Serrano, Anibal</creatorcontrib><creatorcontrib>Torres, Marta</creatorcontrib><creatorcontrib>Almendros, Isaac</creatorcontrib><creatorcontrib>Casitas, Raquel</creatorcontrib><creatorcontrib>Fernández-Navarro, Isabel</creatorcontrib><creatorcontrib>Garcia-Sanchez, Aldara</creatorcontrib><creatorcontrib>Aguirre, Luis A</creatorcontrib><creatorcontrib>Farre, Ramón</creatorcontrib><creatorcontrib>López-Collazo, Eduardo</creatorcontrib><creatorcontrib>García-Rio, Francisco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The European respiratory journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cubillos-Zapata, Carolina</au><au>Avendaño-Ortiz, Jose</au><au>Hernandez-Jimenez, Enrique</au><au>Toledano, Victor</au><au>Casas-Martin, Jose</au><au>Varela-Serrano, Anibal</au><au>Torres, Marta</au><au>Almendros, Isaac</au><au>Casitas, Raquel</au><au>Fernández-Navarro, Isabel</au><au>Garcia-Sanchez, Aldara</au><au>Aguirre, Luis A</au><au>Farre, Ramón</au><au>López-Collazo, Eduardo</au><au>García-Rio, Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea</atitle><jtitle>The European respiratory journal</jtitle><addtitle>Eur Respir J</addtitle><date>2017-10</date><risdate>2017</risdate><volume>50</volume><issue>4</issue><spage>1700833</spage><epage>1700833</epage><pages>1700833-1700833</pages><issn>0903-1936</issn><eissn>1399-3003</eissn><abstract>Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8
T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human
and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8
T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8
T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.</abstract><cop>England</cop><pub>European Respiratory Society Journals Ltd</pub><pmid>29051270</pmid><doi>10.1183/13993003.00833-2017</doi><tpages>1</tpages><orcidid>https://orcid.org/&quot;0000-0002-2478-2700</orcidid><orcidid>https://orcid.org/&quot;0000-0003-0903-9385</orcidid><orcidid>https://orcid.org/0000-0002-2478-2700</orcidid><orcidid>https://orcid.org/0000-0003-0903-9385</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Animal models Apnea Apoptosis B7-H1 Antigen - metabolism Cancer CD8 antigen CD8-Positive T-Lymphocytes - physiology Cell activation Cell death Cell proliferation Cytotoxicity Female Gene Expression Regulation Humans Hypoxia Hypoxia-inducible factors Lymphocytes T Male Middle Aged Monocytes Monocytes - physiology PD-1 protein PD-L1 protein Programmed Cell Death 1 Receptor - metabolism Retinoic acid Signal Transduction Sleep Sleep apnea Sleep Apnea, Obstructive - diagnosis Sleep Apnea, Obstructive - metabolism Sleep disorders Suppressor cells T cell receptors Transfection Tumors Up-Regulation |
| title | Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea |
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