Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality

被引:150
作者
Saha, Asim [1 ,2 ]
Aoyama, Kazutoshi [1 ,2 ]
Taylor, Patricia A. [1 ,2 ]
Koehn, Brent H. [1 ,2 ]
Veenstra, Rachelle G. [1 ,2 ]
Panoskaltsis-Mortari, Angela [1 ,2 ]
Munn, David H. [3 ]
Murphy, William J. [4 ]
Azuma, Miyuki [5 ]
Yagita, Hideo [6 ]
Fife, Brian T. [7 ,8 ]
Sayegh, Mohammed H. [9 ]
Najafian, Nader [9 ]
Socie, Gerard [10 ,11 ]
Ahmed, Rafi [12 ,13 ]
Freeman, Gordon J. [14 ]
Sharpe, Arlene H. [15 ,16 ]
Blazar, Bruce R. [1 ,2 ]
机构
[1] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA
[3] Med Coll Georgia, Dept Pediat, Sch Med, Augusta, GA 30912 USA
[4] Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA
[5] Tokyo Med & Dent Univ, Dept Mol Immunol, Tokyo, Japan
[6] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan
[7] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA
[8] Univ Minnesota, Ctr Immunol, Minneapolis, MN 55455 USA
[9] Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA 02115 USA
[10] Univ Paris 07, Hop St Louis, AP HP, Serv Hematol Greffe, Paris, France
[11] Unite Inst Natl Sante & Rech Med U940, Paris, France
[12] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA
[13] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[14] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[15] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA
[16] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
T-CELL-ACTIVATION; TNF-ALPHA; PD-1; TOLERANCE; RECEPTOR; PHOSPHORYLATION; LYMPHOCYTES; ENGAGEMENT; INHIBITOR; INTEGRINS;
D O I
10.1182/blood-2013-05-500801
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, play an important role in the maintenance of peripheral tolerance. We explored the role of PD-1 ligands in regulating graft-versus-host disease (GVHD). Both PD-L1 and PD-L2 expression were upregulated in the spleen, liver, colon, and ileum of GVHD mice. Whereas PD-L2 expression was limited to hematopoietic cells, hematopoietic and endothelial cells expressed PD-L1. PD-1/PD-L1, but not PD-1/PD-L2, blockade markedly accelerated GVHD-induced lethality. Chimera studies suggest that PD-L1 expression on host parenchymal cells is more critical than hematopoietic cells in regulating acute GVHD. Rapid mortality onset in PD-L1-deficient hosts was associated with increased gut T-cell homing and loss of intestinal epithelial integrity, along with increased donor T-cell proliferation, activation, Th1 cytokine production, and reduced apoptosis. Bioenergetics profile analysis of proliferating alloreactive donor T-cells demonstrated increased aerobic glycolysis and oxidative phosphorylation in PD-L1-deficient hosts. Donor T-cells exhibited a hyperpolarized mitochondrial membrane potential, increased superoxide production, and increased expression of a glucose transporter in PD-L1-deficient hosts. Taken together, these data provide new insight into the differential roles of host PD-L1 and PD-L2 and their associated cellular and metabolic mechanisms controlling acute GVHD.
引用
收藏
页码:3062 / 3073
页数:12
相关论文
共 50 条
[31]   Progress in programmed cell death-1/programmed cell death-ligand 1 pathway inhibitors and binding mode analysis [J].
Li, Xiaoyun ;
Zeng, Qin ;
Xu, Fengjiao ;
Jiang, Yuying ;
Jiang, Zhongmei .
MOLECULAR DIVERSITY, 2023, 27 (04) :1935-1955
[32]   Programmed death ligand 1 is over-expressed by neutrophils in the blood of patients with active tuberculosis [J].
McNab, Finlay W. ;
Berry, Matthew P. R. ;
Graham, Christine M. ;
Bloch, Susannah A. A. ;
Oni, Tolu ;
Wilkinson, Katalin A. ;
Wilkinson, Robert J. ;
Kon, Onn M. ;
Banchereau, Jacques ;
Chaussabel, Damien ;
O'Garra, Anne .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2011, 41 (07) :1941-1947
[33]   The Programmed Cell Death Ligand-1/Programmed Cell Death-1 Pathway Mediates Pregnancy-Induced Analgesia via Regulating Spinal Inflammatory Cytokines [J].
Tan, HuiLing ;
Ding, ZhenDong ;
Zhang, ChengLiang ;
Yan, JianQin ;
Yang, Yong ;
Li, Ping .
ANESTHESIA AND ANALGESIA, 2021, 133 (05) :1321-1330
[34]   Programmed Death Ligand 2 in Cancer-Induced Immune Suppression [J].
Rozali, Esdy N. ;
Hato, Stanleyson V. ;
Robinson, Bruce W. ;
Lake, Richard A. ;
Lesterhuis, W. Joost .
CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2012,
[35]   Programmed death ligand-1 expression in non-small cell lung cancer [J].
Velcheti, Vamsidhar ;
Schalper, Kurt A. ;
Carvajal, Daniel E. ;
Anagnostou, Valsamo K. ;
Syrigos, Konstantinos N. ;
Sznol, Mario ;
Herbst, Roy S. ;
Gettinger, Scott N. ;
Chen, Lieping ;
Rimm, David L. .
LABORATORY INVESTIGATION, 2014, 94 (01) :107-116
[36]   T-Cell Infiltration and Clonality Correlate With Programmed Cell Death Protein 1 and Programmed Death-Ligand 1 Expression in Patients With Soft Tissue Sarcomas [J].
Pollack, Seth M. ;
He, Qianchuan ;
Yearley, Jennifer H. ;
Emerson, Ryan ;
Vignali, Marissa ;
Zhang, Yuzheng ;
Redman, Mary W. ;
Baker, Kelsey K. ;
Cooper, Sara ;
Donahue, Bailey ;
Loggers, Elizabeth T. ;
Cranmer, Lee D. ;
Spraker, Matthew B. ;
Seo, Y. David ;
Pillarisetty, Venu G. ;
Ricciotti, Robert W. ;
Hoch, Benjamin L. ;
McClanahan, Terrill K. ;
Murphy, Erin ;
Blumenschein, Wendy M. ;
Townson, Steven M. ;
Benzeno, Sharon ;
Riddell, Stanley R. ;
Jones, Robin L. .
CANCER, 2017, 123 (17) :3291-3304
[37]   Reduced expression of programmed cell death 1 and programmed cell death ligand 1 in infiltrating inflammatory cells of lichen planus without administration of immune checkpoint inhibitors [J].
Shirouchi, Kazufumi ;
Koshikawa, Sachiko ;
Shinya, Koichiro ;
Watanabe, Hideaki ;
Izumi, Miki ;
Yoshimura, Kiyoshi ;
Sueki, Hirohiko .
JOURNAL OF DERMATOLOGY, 2021, 48 (09) :1428-1432
[38]   Increasing the expression of programmed death ligand 2 (PD-L2) but not 4-1BB ligand in colorectal cancer cells [J].
Shakerin, Parastoo ;
Moghadam, Bijan Sedighi ;
Baghaei, Kaveh ;
Naraghi, Zahra Safaei ;
Hesari, Kambiz Kamyab ;
Aghdaei, Hamid Asadzadeh ;
Shoormasti, Raheleh Shokouhi ;
Fazeli, Mohammad Sadegh ;
Nourizadeh, Maryam .
MOLECULAR BIOLOGY REPORTS, 2020, 47 (08) :5689-5697
[39]   Fragment-based screening of programmed death ligand 1 (PD-L1) [J].
Perry, Evan ;
Mills, Jonathan J. ;
Zhao, Bin ;
Wang, Feng ;
Sun, Qi ;
Christov, Plamen P. ;
Tarr, James C. ;
Rietz, Tyson A. ;
Olejniczak, Edward T. ;
Lee, Taekyu ;
Fesik, Stephen .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (06) :786-790
[40]   Donor and host B7-H4 expression negatively regulates acute graft-versus-host disease lethality [J].
Saha, Asim ;
Taylor, Patricia A. ;
Lees, Christopher J. ;
Panoskaltsis-Mortari, Angela ;
Osborn, Mark J. ;
Feser, Colby J. ;
Thangavelu, Govindarajan ;
Melchinger, Wolfgang ;
Refaeli, Yosef ;
Hill, Geoffrey R. ;
Munn, David H. ;
Murphy, William J. ;
Serody, Jonathan S. ;
Maillard, Ivan ;
Kreymborg, Katharina ;
van den Brink, Marcel ;
Dong, Chen ;
Huang, Shuyu ;
Zang, Xingxing ;
Allison, James P. ;
Zeiser, Robert ;
Blazar, Bruce R. .
JCI INSIGHT, 2019, 4 (19)