{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:09:39Z","timestamp":1791083379720,"version":"4.1.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fight for Sight Denmark"},{"name":"Region Zealand's research promotion fund"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>Peripheral T cell CXCR3 expression has been found uniquely lower in patients having neovascular age-related macular degeneration (nAMD) than in healthy individuals. The CXCR3-axis has been shown to have angiostatic and antifibrotic properties. We have recently investigated systemic markers in patients with myeloproliferative neoplasms (MPNs) because of their higher prevalence of AMD, and we have observed higher systemic chronic low-grade inflammation and immunosenescence signs in MPNs with drusen (MPNd) compared to those with normal retinas (MPNn). The MPNs evolve in a biological continuum from early cancer-stages (essential thrombocytosis, polycythemia vera) to the advanced myelofibrosis stage. Especially myelofibrosis is characterized by bone marrow angiogenesis and fibrosis, similarly to retinal observations in nAMD. We speculate if we can find lower CXCR3 expression in MPNs, particularly myelofibrosis and if differences are seen between MPNd and MPNn. We also wanted to compare expression in nAMD and intermediate (i)AMD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients in this cross-sectional study were 29 nAMD, 28 iAMD, 35 MPNd, and 27 MPNn. We performed flowcytometry on blood to measure CXCR3 expression.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>CD8+CXCR3 expression in nAMD was 6,1%, significantly lower than in iAMD 16%, MPNd 11%, MPNn 12% (p-values&lt;0.05). Similar results were seen for CD4+CXCR3 expression. We also found CXCR3 expression decreasing over the MPN-continuum. For instance, in myelofibrosis, intermediate monocytes expression was 6.2%, significantly lower than 18% in ET and 18% in PV (p-values&lt;0.05).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We find CXCR3 downregulation on T-cells and some monocyte subset in nAMD compared to iAMD, MPNd, and MPNn, in line with previous nAMD studies. We also find CXCR3 downregulation in most monocyte subsets over the MPN continuum. Systemic leukocyte CXCR3 expression could both be involved in changes seen in the retina and the bone marrow. Further understanding the CXCR3-axis in AMD and MPNs may elucidate underlying pathogenic mechanisms and reveal new targets for treatment.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0269960","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T17:37:47Z","timestamp":1655401067000},"page":"e0269960","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lower CXCR3 expression in both patients with neovascular AMD and advanced stages of chronic myeloproliferative blood cancers"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-6027","authenticated-orcid":true,"given":"Charlotte","family":"Liisborg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-7826","authenticated-orcid":true,"given":"Vibe","family":"Skov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Kj\u00e6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Carl","family":"Hasselbalch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Lykke S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"pone.0269960.ref001","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration.","volume":"7","author":"M Fleckenstein","year":"2021","journal-title":"Nat Rev Dis Prim"},{"key":"pone.0269960.ref002","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.ophtha.2012.10.036","article-title":"Clinical classification of age-related macular degeneration","volume":"120","author":"FL Ferris","year":"2013","journal-title":"Ophthalmology"},{"key":"pone.0269960.ref003","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0039-6257(03)00030-4","article-title":"Age-related macular degeneration: Etiology, pathogenesis, and therapeutic strategies.","volume":"48","author":"J Ambati","year":"2003","journal-title":"Surv Ophthalmol"},{"key":"pone.0269960.ref004","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ebiom.2018.11.029","article-title":"Myofibroblasts in macular fibrosis secondary to neovascular age-related macular degeneration\u2014the potential sources and molecular cues for their recruitment and activation.","volume":"38","author":"K Little","year":"2018","journal-title":"EBioMedicine"},{"key":"pone.0269960.ref005","author":"P Romagnani","journal-title":"CXC chemokines: the regulatory link between inflammation and angiogenesis n.d"},{"key":"pone.0269960.ref006","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.yexcr.2010.12.017","article-title":"CXCR3 in T cell function","volume":"317","author":"JR Groom","year":"2011","journal-title":"Exp Cell Res"},{"key":"pone.0269960.ref007","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/icb.2010.158","article-title":"CXCR3 ligands: redundant, collaborative and antagonistic functions","volume":"89","author":"JR Groom","year":"2011","journal-title":"Immunol Cell Biol"},{"key":"pone.0269960.ref008","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJM199802123380706","article-title":"Chemokines\u2014Chemotactic Cytokines That Mediate Inflammation","volume":"338","author":"AD Luster","year":"1998","journal-title":"N Engl J Med"},{"key":"pone.0269960.ref009","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/BF03345149","article-title":"Role for interferon-gamma inducible chemokines in endocrine autoimmunity: an expanding field","volume":"26","author":"M Rotondi","year":"2003","journal-title":"J Endocrinol Invest"},{"key":"pone.0269960.ref010","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3389\/fmed.2018.00271","article-title":"The Role of CXCR3 and Its Chemokine Ligands in Skin Disease and Cancer.","volume":"5","author":"PT Kuo","year":"2018","journal-title":"Front Med"},{"key":"pone.0269960.ref011","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.yexcr.2010.10.020","article-title":"Chemokines as mediators of tumor angiogenesis and neovascularization","volume":"317","author":"EC Keeley","year":"2011","journal-title":"Exp Cell Res"},{"key":"pone.0269960.ref012","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3389\/fimmu.2020.00976","article-title":"CXCR3 Ligands in Cancer and Autoimmunity, Chemoattraction of Effector T Cells, and Beyond.","volume":"11","author":"N. 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