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Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance
Open accessAbstract
Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4+CD25+FoxP3+ T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.
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“To this end, PD-L1111 or FasL112,113 proteins were immobilized onto the surface of poly(ethylene glycol) microgels, which were then mixed together with allogeneic islets and co-transplanted into either mice111,112 or non-human primates113. In conjunction with a transient rapamycin treatment, these functionalized microgels greatly improved islet survival without the need for long-term immunosuppres”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [112]
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Cites
Fas Ligand-Induced Apoptosis as a Mechanism of Immune Privilege
Griffith, T. S., Brunner, T., Fletcher, S. M., Green, D. R., & Ferguson, T. A. (1995) · Science · doi:10.1126/science.270.5239.1189 · Cited by 1,990
International trial of the Edmonton protocol for islet transplantation
Shapiro, A. M. J., Ricordi, C., Hering, B. J., Auchincloss, H., Lindblad, R., Robertson, R. P., Secchi, A., Brendel, M. D., Berney, T., Brennan, D. C., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061267 · Cited by 1,942
Lethal effect of the anti-Fas antibody in mice
Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., & Nagata, S. (1993) · Nature · doi:10.1038/364806a0 · Cited by 1,881
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
Kim, J. M., Rasmussen, J. P., & Rudensky, A. Y. (2006) · Nature Immunology · doi:10.1038/ni1428 · Cited by 1,827
Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation
Ju, S., Panka, D., Cui, H., Ettinger, R., EI-Khatib, M., Sherr, D., Stanger, B., & Marshak-Rothstein, A. (1995) · Nature · doi:10.1038/373444a0 · Cited by 1,709
mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575
Brunner, T., Mogil, R. J., LaFace, D., Yoo, N. J., Mahboubi, A., Echeverri, F., Martin, S. J., Force, W. R., Lynch, D. H., Ware, C. F., et al. (1995) · Nature · doi:10.1038/373441a0 · Cited by 1,314
Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells.
Battaglia, M., Stabilini, A., & Roncarolo, M. (2005) · Blood · doi:10.1182/blood-2004-10-3932 · Cited by 1,203
Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease
Lahl, K., Loddenkemper, C., Drouin, C. E., Freyer, J., Arnason, J. E., Eberl, G., Hamann, A., Wagner, H., Huehn, J., & Sparwasser, T. D. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061852 · Cited by 951
Rao, R. R., Li, Q., Odunsi, K., & Shrikant, P. A. (2010) · Immunity · doi:10.1016/j.immuni.2009.10.010 · Cited by 656
Phelps, E. A., Enemchukwu, N. O., Fiore, V. F., Sy, J. C., Murthy, N., Sulchek, T., Barker, T. H., & García, A. J. (2011) · Advanced Materials · doi:10.1002/adma.201103574 · Cited by 550
Self-citationKang, S.-M., Schneider, D. B., Lin, Z., Hanahan, D., Dichek, D. A., Stock, P. G., & Bækkeskov, S. (1997) · Nature Medicine · doi:10.1038/nm0797-738 · Cited by 448
Prevention of Islet Allograft Rejection with Engineered Myoblasts Expressing FasL in Mice
Lau, H. T., Yu, M., Fontana, A., & Stoeckert, C. J. (1996) · Science · doi:10.1126/science.273.5271.109 · Cited by 445
CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival.
Stuart, P. M., Griffith, T. S., Usui, N., Pepose, J., Yu, X.-H., & Ferguson, T. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119173 · Cited by 406
Zeiser, R., Leveson-Gower, D. B., Zambricki, E. A., Kambham, N., Beilhack, A., Loh, J., Hou, J.-Z., & Negrin, R. S. (2008) · Blood · doi:10.1182/blood-2007-06-094482 · Cited by 402
Membrane-bound Fas ligand only is essential for Fas-induced apoptosis
O’ Reilly, L. A., Tai, L., Lee, L., Kruse, E. A., Grabow, S., Fairlie, W. D., Haynes, N. M., Tarlinton, D. M., Zhang, J.-G., Belz, G. T., et al. (2009) · Nature · doi:10.1038/nature08402 · Cited by 400
Acceleration of Diabetes in Young Nod Mice with a CD4 + Islet-specific T Cell Clone
HASKINS, K. M., & MCDUFFIE, M. J. (1990) · Science · doi:10.1126/science.2205920 · Cited by 386
Control of Autoimmune Diabetes in NOD Mice by GAD Expression or Suppression in β Cells
Yoon, J.-W., Yoon, C.-S., Lim, H.-W., Huang, Q. Q., KANG, Y. Y., Pyun, K. H., Hirasawa, K., Sherwin, R. S., & Jun, H. (1999) · Science · doi:10.1126/science.284.5417.1183 · Cited by 247
Min, W., Gorczynski, R. M., Huang, X., Kushida, M. M., Kim, P., Obataki, M., Lei, J., Suri, R. M., & Cattral, M. S. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.1.161 · Cited by 236
Headen, D. M., Aubry, G., Lu, H., & García, A. J. (2014) · Advanced Materials · doi:10.1002/adma.201304880 · Cited by 207
Self-citationT-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins
Roep, B. O., Arden, S. D., de vries, R. R. P., & Hutton, J. C. (1990) · Nature · doi:10.1038/345632a0 · Cited by 185
Roep, B. O., Stobbe, I., Duinkerken, G., ROOD, J. J. V., Lernmark, Å., Keymeulen, B., PIPELEERS, D. G., Claas, F. H. J., & de Vries, R. R. (1999) · Diabetes · doi:10.2337/diabetes.48.3.484 · Cited by 184
Basu, S., Golovina, T. N., Mikheeva, T., June, C. H., & Riley, J. L. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.9.5794 · Cited by 183
Soluble Fas Ligand Is Chemotactic for Human Neutrophilic Polymorphonuclear Leukocytes
Ottonello, L. C., Tortolina, G., Amelotti, M., & Dallegri, F. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.6.3601 · Cited by 177
Phelps, E. A., Headen, D. M., Taylor, W. R., Thulé, P. M., & Garcı́a, A. J. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.012 · Cited by 170
Self-citationWeaver, J. D., Headen, D. M., Aquart, J., Johnson, C. T., Shea, L. D., Shirwan, H., & García, A. J. (2017) · Science Advances · doi:10.1126/sciadv.1700184 · Cited by 170
Self-citationBioengineering of an Intraabdominal Endocrine Pancreas
Baidal, D. A., Ricordi, C., Berman, D. M., Alvarez, A., Padilla, N., Ciancio, G., Linetsky, E., Pileggi, A., & Alejandro, R. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1613959 · Cited by 160
Induction of antigen-specific immunosuppression by CD95L cDNA-transfected 'killer' dendritic cells
Matsue, H., Matsue, K., Walters, M., Okumura, K., Yagita∥, H., & Takashima, A. (1999) · Nature Medicine · doi:10.1038/11375 · Cited by 157
Long-Term Function (6 Years) of Islet Allografts in Type 1 Diabetes
Alejandro, R., Lehmann, R., Ricordi, C., Kenyon, N. S., Angelico, M. C., Burke, G. W., Esquenazi, V., Nery, J., Betancourt, A., Kong, S. S., et al. (1997) · Diabetes · doi:10.2337/diab.46.12.1983 · Cited by 153
Hurez, V. J., Dao, V. A., Liu, A., Pandeswara, S., Gelfond, J., Sun, L., Bergman, M. A., Orihuela, C. J., Galván, V., Padron, A. S., et al. (2015) · Aging Cell · doi:10.1111/acel.12380 · Cited by 129
Berman, D., Molano, R., Fotino, C., Ulissi, U., Gimeno, J., Mendez, A. J., Kenyon, N., Kenyon, N. S., Andrews, D. M., Ricordi, C., et al. (2016) · Diabetes · doi:10.2337/db15-1525 · Cited by 129
Bunnag, S., Allanach, K., Jhangri, G. S., Sis, B., Einecke, G., Mengel, M., Mueller, T., & Halloran, P. F. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02268.x · Cited by 128
Yellen, P., Saqcena, M., Salloum, D., Feng, J., Preda, A., Xu, L., Rodrik-Outmezguine, V. S., & Foster, D. A. (2011) · Cell Cycle · doi:10.4161/cc.10.22.18124 · Cited by 117
Priming and effector dependence on insulin B:9–23 peptide in NOD islet autoimmunity
Nakayama, M., Beilke, J. N., Jasinski, J., Kobayashi, M., Miao, D., Li, M., Coulombe, M., Liu, E., Elliott, J. F., Gill, R. G., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31368 · Cited by 109
Cell Membrane Modification for Rapid Display of Proteins as a Novel Means of Immunomodulation
Yolcu, E. S., Askenasy, N., Singh, N. P., Lamhamedi-Cherradi, S.-E., & Shirwan, H. (2002) · Immunity · doi:10.1016/s1074-7613(02)00482-x · Cited by 98
Self-citationRadu, R. G., Fujimoto, S., Mukai, E., Takehiro, M., Shimono, D., Nabe, K., Shimodahira, M., Kominato, R., Aramaki, Y., Nishi, Y., et al. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00390.2004 · Cited by 85
Yolcu, E. S., Zhao, H., Bandura-Morgan, L., Lacelle, C., Woodward, K. B., Askenasy, N., & Shirwan, H. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003266 · Cited by 82
Self-citationInhibition of the alloantibody response by CD95 ligand
Arai, H., Chanz, S. Y., Bishop, D. K., & Nabel, G. J. (1997) · Nature Medicine · doi:10.1038/nm0897-843 · Cited by 81
Apoptosis as a mechanism of T‐regulatory cell homeostasis and suppression
Yolcu, E. S., Ash, S., Kaminitz, A., Sagiv, Y., Askenasy, N., & Yarkoni, S. (2008) · Immunology and Cell Biology · doi:10.1038/icb.2008.62 · Cited by 65
Self-citationHernández-Fisac, I., Pizarro‐Delgado, J., Calle, C., Marqués, M., Sánchez, A., Barrientos, A., & Tamarit‐Rodriguez, J. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01946.x · Cited by 58
Takeda, Y., Gotoh, M., Dono, K., Nishihara, M., Grochowiecki, T., Kimura, F., Yoshida, T., Ohta, Y., Ota, H., Ohzato, H., et al. (1998) · Diabetologia · doi:10.1007/s001250050909 · Cited by 57
Boggi, U., Vistoli, F., Amorese, G., GIANNARELLI, R., Coppelli, A., Mariotti, R., Rondinini, L., Barsotti, M., Signori, S., Lio, N. D., et al. (2012) · Transplantation · doi:10.1097/tp.0b013e318247a782 · Cited by 50
Tourneur, L., Malassagne, B., Batteux, F., Fabrè, M., Mistou, S., Lallemand, E., Lorès, P., & Chiocchia, G. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1338 · Cited by 34
Yapici, Ü., Bemelman, F. J., Scheepstra, C. G., Roelofs, J. J. T. H., Claessen, N., van der Loos, C. M., der Pant, K. A. M. I. V. D., Bouts, A. H. M., Idu, M. M., Rowshani, A. T., et al. (2009) · Transplantation · doi:10.1097/tp.0b013e3181a24a4b · Cited by 28
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Zhang, K., Feng, Q., Fang, Z., Gu, L., & Bian, L. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00071 · Cited by 401
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Metadata
- Authors
- Headen, D. M., Woodward, K. B., Coronel, M. M., Shrestha, P., Weaver, J. D., Zhao, H., Tan, M., Hunckler, M. D., Bowen, W. S., Johnson, C. T., Shea, L., Yolcu, E. S., García, A. J., & Shirwan, H.
- Affiliations
- Georgia Institute of Technology (US)
- University of Louisville (US)
- Corresponding author
- Shirwan, Haval
- ORCID
- Venue
- Nature Materials
- Published
- 2018-06-04
- Volume
- 17
- Issue
- 8
- Pages
- 732-739
- ISSN
- 1476-1122 (ISSN-L)
- 1476-4660
- PMC
- PMC6060019
- OpenAlex
- W2807344337
- Cited by
- 175
- References
- 44
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 29 · 2023: 27 · 2022: 24 · 2021: 25 · 2020: 16 · 2019: 23 · 2018: 7
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Materials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (4t90dk097787-05, 1s10od016264-01a1)
- National Institute of General Medical Sciences (T32GM008169)
- National Institute of Allergy and Infectious Diseases (R21AI113348, U01AI132817, R56AI121281)
- National Institute of Diabetes and Digestive and Kidney Diseases (T90-DK097787, P30DK020572)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (F30AR069472)
- National Institute of Biomedical Imaging and Bioengineering (R21EB020107)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- islet transplantation, type 1 diabetes, allograft rejection, Fas ligand, microgels, streptavidin, rapamycin, regulatory T cells, effector T cells, immune privilege, biomaterials, graft acceptance
- MeSH terms
- Animals, Biocompatible Materials, Transplantation, Homologous, Islets of Langerhans Transplantation, Streptavidin, Mice, Fas Ligand Protein, Immunomodulation
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