The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8 + T-Cell–Mediated Injury in the Heart
Abstract
Background— PD-L1 and PD-L2 are ligands for the inhibitory receptor programmed death-1 (PD-1), which is an important regulator of immune responses. PD-L1 is induced on cardiac endothelial cells under inflammatory conditions, but little is known about its role in regulating immune injury in the heart. Methods and Results— Cytotoxic T-lymphocyte–mediated myocarditis was induced in mice, and the influence of PD-L1 signaling was studied with PD-L1/L2–deficient mice and blocking antibodies. During cytotoxic T-lymphocyte–induced myocarditis, the upregulation of PD-L1 on cardiac endothelia was dependent on T-cell–derived interferon-γ, and blocking of interferon-γ signaling worsened disease. Genetic deletion of both PD-1 ligands [ PD-L1/2 (−/−) ], as well as treatment with PD-L1 blocking antibody, transformed transient myocarditis to lethal disease, in association with widespread polymorphonuclear leukocyte–rich microabscesses but without change in cytotoxic T-lymphocyte recruitment. PD-L1/2 (−/−) mice reconstituted with bone marrow from wild-type mice remained susceptible to severe disease, which demonstrates that PD-L1 on non–bone marrow–derived cells confers the protective effect. Finally, depletion of polymorphonuclear leukocytes reversed the enhanced susceptibility to lethal myocarditis attributable to PD-L1 deficiency. Conclusions— Myocardial PD-L1, mainly localized on endothelium, is critical for control of immune-mediated cardiac injury and polymorphonuclear leukocyte inflammation.
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Cites
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955
Self-citationOkazaki, T., Tanaka, Y., Nishio, R., Mitsuiye, T., Mizoguchi, A., Wang, J., Ishida, M., Hiai, H., Matsumori, A., Minato, N., et al. (2003) · Nature Medicine · doi:10.1038/nm955 · Cited by 689
Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells
Eppihimer, M., Gunn, J., Freeman, G., Greenfield, E., Chernova, T., Erickson, J., & Leonard, J. (2002) · Microcirculation · doi:10.1080/713774061 · Cited by 272
Self-citationFairweather, D., Frisancho-Kiss, S., Yusung, S. A., Barrett, M. A., Davis, S. E., Gatewood, S. J. L., Njoku, D. B., & Rose, N. R. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63241-5 · Cited by 198
Fairweather, D., Frisancho-Kiss, S., Yusung, S. A., Barrett, M. A., Davis, S. E., Steele, R. A., Gatewood, S. J. L., & Rose, N. R. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.1.261 · Cited by 133
Cited by
PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Self-citationFulminant Myocarditis with Combination Immune Checkpoint Blockade
Johnson, D. B., Balko, J. M., Compton, M. L., Chalkias, S., Gorham, J., Xu, Y., Hicks, M., Puzanov, I., Alexander, M. R., Bloomer, T. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1609214 · Cited by 2,308
Self-citationThe PD‐1 pathway in tolerance and autoimmunity
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00923.x · Cited by 2,300
Self-citationImmune-checkpoint inhibitors: long-term implications of toxicity
Johnson, D. B., Nebhan, C. A., Moslehi, J. J., & Balko, J. M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00600-w · Cited by 982
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Del Re, D. P., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 961
Metadata
- Authors
- Grabie, N., Gotsman, I., DaCosta, R., Pang, H., Stavrakis, G., Butte, M. J., Keir, M. E., Freeman, G. J., Sharpe, A. H., & Lichtman, A. H.
- Venue
- Circulation
- Published
- 2007-10-30
- Volume
- 116
- Issue
- 18
- Pages
- 2062-2071
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1986954791
- Cited by
- 288
- References
- 5
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8 + T-Cell–Mediated Injury in the Heart. https://app.cochat.ai/papers/10.1161/circulationaha.107.709360
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- Grabie, N., Gotsman, I., DaCosta, R., Pang, H., Stavrakis, G., Butte, M. J., Keir, M. E., Freeman, G. J., Sharpe, A. H., & Lichtman, A. H. (2007). Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8 + T-Cell–Mediated Injury in the Heart. Circulation. https://doi.org/10.1161/circulationaha.107.709360
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