{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:10:31Z","timestamp":1794003031804,"version":"4.8.0"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"5","funder":[{"name":"NIH","award":["NIH R01 HL051014"],"award-info":[{"award-number":["NIH R01 HL051014"]}]},{"name":"NIH","award":["F31-HL129563"],"award-info":[{"award-number":["F31-HL129563"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,3,8]]},"abstract":"<jats:p>\n                    Early acute rejection of human allografts is mediated by circulating alloreactive host effector memory T cells (T\n                    <jats:sub>EM<\/jats:sub>\n                    ). T\n                    <jats:sub>EM<\/jats:sub>\n                    infiltration typically occurs across graft postcapillary venules and involves sequential interactions with graft-derived endothelial cells (ECs) and pericytes (PCs). While the role of ECs in allograft rejection has been extensively studied, contributions of PCs to this process are largely unknown. This study aimed to characterize the effects and mechanisms of interactions between human PCs and allogeneic T\n                    <jats:sub>EM<\/jats:sub>\n                    . We report that unstimulated PCs, like ECs, can directly present alloantigen to T\n                    <jats:sub>EM<\/jats:sub>\n                    , but while IFN-\u03b3\u2013activated ECs (\u03b3-ECs) show increased ability to stimulate alloreactive T cells, IFN-\u03b3\u2013activated PCs (\u03b3-PCs) instead suppress T\n                    <jats:sub>EM<\/jats:sub>\n                    proliferation but not cytokine production or signaling. RNA sequencing analysis of PCs, \u03b3-PCs, ECs, and \u03b3-ECs reveal induction of indoleamine 2,3-dioxygenase 1 (IDO1) in \u03b3-PCs to significantly higher levels than in \u03b3-ECs that correlates with tryptophan depletion in vitro. Consistently, shRNA knockdown of IDO1 markedly reduces \u03b3-PC\u2013mediated immunoregulatory effects. Furthermore, human PCs express IDO1 in a skin allograft rejection humanized mouse model and in human renal allografts with acute T cell\u2013mediated rejection. We conclude that immunosuppressive properties of human PCs are not intrinsic but instead result from IFN-\u03b3\u2013induced IDO1-mediated tryptophan depletion.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.97881","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T11:02:53Z","timestamp":1520420573000},"source":"Crossref","is-referenced-by-count":25,"title":["Interferon-\u03b3 converts human microvascular pericytes into negative regulators of alloimmunity through induction of indoleamine 2,3-dioxygenase 1"],"prefix":"10.1172","volume":"3","author":[{"given":"Rebecca","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-1893","authenticated-orcid":true,"given":"Jonathan","family":"Merola","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Manes","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfeng","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory T.","family":"Tietjen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-9822","authenticated-orcid":true,"given":"Francesc","family":"L\u00f3pez-Gir\u00e1ldez","sequence":"additional","affiliation":[{"name":"Yale Center for Genome Analysis, Yale University, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Broecker","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Addenbrooke\u2019s Hospital, Cambridge University Hospitals, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caodi","family":"Fang","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy C.","family":"Kirkiles-Smith","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Jane-Wit","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan S.","family":"Pober","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,3,8]]},"reference":[{"issue":"4","key":"B1","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.4049\/jimmunol.163.4.2267","article-title":"Pretransplant frequency of donor-specific, IFN-gamma-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes","volume":"163","author":"Heeger","year":"1999","journal-title":"J Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4397"},{"issue":"8","key":"B3","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a014993","article-title":"Origin and biology of the allogeneic response","volume":"3","author":"Lakkis","year":"2013","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.4886"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00116-9"},{"issue":"1 Suppl","key":"B6","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1097\/01.tp.0000231356.57576.82","article-title":"Endothelial cell-T lymphocyte interactions: IP[corrected]-10 stimulates rapid transendothelial migration of human effector but not central memory CD4+ T cells. Requirements for shear stress and adhesion molecules","volume":"82","author":"Manes","year":"2006","journal-title":"Transplantation"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111622"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300280"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.217117"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198106000-00005"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.157.4.1339"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.21.6641"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.306290"},{"issue":"1","key":"B14","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.85293","article-title":"Blocking MHC class II on human endothelium mitigates acute rejection","volume":"1","author":"Abrahimi","year":"2016","journal-title":"JCI Insight"},{"issue":"12","key":"B15","doi-asserted-by":"crossref","first-page":"5402","DOI":"10.4049\/jimmunol.153.12.5402","article-title":"Antigen-presenting function of human endothelial cells. Direct activation of resting CD8 T cells","volume":"153","author":"Epperson","year":"1994","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.091003.090312"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1849"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.19.9146"},{"issue":"5","key":"B19","first-page":"367","article-title":"Explant outgrowth, propagation and characterization of human pericytes","volume":"17","author":"Maier","year":"2010","journal-title":"Microcirculation"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.12.001"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nri3641"},{"issue":"1","key":"B22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/ni.2477","article-title":"Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and \u2018instruct\u2019 them with pattern-recognition and motility programs","volume":"14","author":"Stark","year":"2013","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600138"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8008"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.149"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903670"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05241.x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2014-0097"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2A0516-239R"},{"issue":"1","key":"B30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4049\/jimmunol.156.1.5","article-title":"Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE)","volume":"156","author":"Ferber","year":"1996","journal-title":"J Immunol"},{"issue":"11","key":"B31","doi-asserted-by":"crossref","first-page":"5507","DOI":"10.4049\/jimmunol.158.11.5507","article-title":"Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice","volume":"158","author":"Vermeire","year":"1997","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119787"},{"issue":"5","key":"B33","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.4049\/jimmunol.160.5.2059","article-title":"IFN-gamma is critical for long-term allograft survival induced by blocking the CD28 and CD40 ligand T cell costimulation pathways","volume":"160","author":"Konieczny","year":"1998","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63960-0"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-6143.2003.00153.x"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63845-X"},{"issue":"5","key":"B37","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.4049\/jimmunol.153.5.2204","article-title":"IFN-gamma selectively inhibits lipopolysaccharide-inducible JE\/monocyte chemoattractant protein-1 and KC\/GRO\/melanoma growth-stimulating activity gene expression in mouse peritoneal macrophages","volume":"153","author":"Ohmori","year":"1994","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2003.07.003"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.03.070"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198909000-00011"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199307000-00012"},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2012.00054","article-title":"Key features of the intragraft microenvironment that determine long-term survival following transplantation","volume":"3","author":"Bruneau","year":"2012","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1126\/science.6635659"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.12.8386"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002835"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp120"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1621"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/97881\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:02:49Z","timestamp":1779195769000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/97881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,8]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,3,8]]},"published-print":{"date-parts":[[2018,3,8]]}},"alternative-id":["10.1172\/jci.insight.97881"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.97881","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,8]]},"article-number":"e97881"}}