{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:28:21Z","timestamp":1781796501599,"version":"3.54.5"},"reference-count":105,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI143261"],"award-info":[{"award-number":["AI143261"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Allergy and Infectious Diseases T32"},{"name":"Training Program in Immunology","award":["AI074005"],"award-info":[{"award-number":["AI074005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Persistent antigen exposure during chronic viral infection and tumor development drives CD8 T cells into an exhausted, hypofunctional state. Understanding the molecular pathways that enforce T-cell exhaustion is critical for improving current immunotherapies. Previously, we have shown the bioactive lipid lysophosphatidic acid (LPA) regulates CD8 T-cell function through LPA receptor 5 (LPAR5) signaling, including demonstrating that Lpar5\u2013\/\u2013 CD8 T cells exhibit enhanced tumor clearance in murine models of melanoma. Importantly, significantly elevated levels of LPA have been identified in individuals with different cancers and persistent viral infections such as HIV, hepatitis C virus, and hepatitis B virus. To investigate the role of Lpar5 in the differentiation and maintenance of exhausted CD8 T cells, we utilized the lymphocytic choriomeningitis virus (LCMV) infection model. In response to infection with LCMV Clone 13, but not Armstrong, one-quarter of Lpar5\u2013\/\u2013 animals succumbed to infection, and this was accompanied by an increased frequency of LCMV-specific Lpar5\u2013\/\u2013 CD8 T cells maintained in a less terminally exhausted state. Using P14 transgenic mice, we demonstrate that Lpar5 acts in a cell-intrinsic and temporal manner to regulate CD8 T-cell accumulation and exhaustion programming during Clone 13 infection. The enhanced accumulation of Lpar5\u2013\/\u2013 P14 cells during the acute phase of Clone 13 infection appears to be regulated by Lpar5-mediated changes in T-cell survival and not through trafficking or proliferation. RNA sequencing analyses and surface phenotyping show that Lpar5 likely regulates CD8 T-cell exhaustion through modulation of NK receptor expression, including the CD94\/NKG2A inhibitory axis.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf210","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T23:51:21Z","timestamp":1756511481000},"page":"3055-3068","source":"Crossref","is-referenced-by-count":2,"title":["Lpar5 regulates the CD8 T-cell response to persistent virus infection by altering exhaustion programming, survival, and NK receptor expression"],"prefix":"10.1093","volume":"214","author":[{"given":"Marc A","family":"D\u2019Antonio","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C","family":"Ware","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"DiLisio","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jessamine","family":"Michaels","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M","family":"Habenicht","sequence":"additional","affiliation":[{"name":"Office of Laboratory Animal Resources and Department of Pathology, Anschutz Medical Campus , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennett J","family":"Davenport","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pelanda","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO,","place":["United 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