-
Je něco špatně v tomto záznamu ?
Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study
N. Murakami, TJ. Borges, TS. Win, P. Abarzua, S. Tasigiorgos, B. Kollar, V. Barrera, S. Ho Sui, JE. Teague, E. Bueno, RA. Clark, CG. Lian, GF. Murphy, B. Pomahac, LV. Riella
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
Grantová podpora
K08 DK120868
NIDDK NIH HHS - United States
R01 AI143887
NIAID NIH HHS - United States
T32 DK007527
NIDDK NIH HHS - United States
UL1 RR025758
NCRR NIH HHS - United States
- MeSH
- interleukin-2 * aplikace a dávkování imunologie MeSH
- lidé MeSH
- pilotní projekty MeSH
- regulační T-lymfocyty MeSH
- rejekce štěpu MeSH
- transplantace obličeje * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Face transplantation is a life-changing procedure for patients with severe composite facial defects. However, it is hampered by high acute rejection rates due to the immunogenicity of skin allograft and toxicity linked to high doses of immunosuppression. To reduce immunosuppression-associated complications, we, for the first time in face transplant recipients, used low-dose interleukin 2 (IL-2) therapy to expand regulatory T cells (Tregs) in vivo and to enhance immune modulation, under close immunological monitoring of peripheral blood and skin allograft. Low-dose IL-2 achieved a sustained expansion (∼4-fold to 5-fold) of circulating Tregs and a reduction (∼3.5-fold) of B cells. Post-IL-2 Tregs exhibited greater suppressive function, characterized by higher expression of TIM-3 and LAG3co-inhibitory molecules. In the skin allograft, Tregs increased after low-dose IL-2 therapy. IL-2 induced a distinct molecular signature in the allograft with reduced cytotoxicity-associated genes (granzyme B and perforin). Two complications were observed during the trial: one rejection event and an episode of autoimmune hemolytic anemia. In summary, this initial experience demonstrated that low-dose IL-2 therapy was not only able to promote immune regulation in face transplant recipients but also highlighted challenges related to its narrow therapeutic window. More specific targeted Treg expansion strategies are needed to translate this approach to the clinic.
Department of Dermatology Brigham and Women's Hospital Harvard Medical School Boston Maryland USA
Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston Maryland USA
Transplant Research Center Brigham and Women's Hospital Harvard Medical School Boston Maryland USA
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24003199
- 003
- CZ-PrNML
- 005
- 20240509113217.0
- 007
- ta
- 008
- 240220s2023 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.ajt.2023.01.016 $2 doi
- 035 __
- $a (PubMed)36740193
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Murakami, Naoka $u Transplant Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 245 10
- $a Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study / $c N. Murakami, TJ. Borges, TS. Win, P. Abarzua, S. Tasigiorgos, B. Kollar, V. Barrera, S. Ho Sui, JE. Teague, E. Bueno, RA. Clark, CG. Lian, GF. Murphy, B. Pomahac, LV. Riella
- 520 9_
- $a Face transplantation is a life-changing procedure for patients with severe composite facial defects. However, it is hampered by high acute rejection rates due to the immunogenicity of skin allograft and toxicity linked to high doses of immunosuppression. To reduce immunosuppression-associated complications, we, for the first time in face transplant recipients, used low-dose interleukin 2 (IL-2) therapy to expand regulatory T cells (Tregs) in vivo and to enhance immune modulation, under close immunological monitoring of peripheral blood and skin allograft. Low-dose IL-2 achieved a sustained expansion (∼4-fold to 5-fold) of circulating Tregs and a reduction (∼3.5-fold) of B cells. Post-IL-2 Tregs exhibited greater suppressive function, characterized by higher expression of TIM-3 and LAG3co-inhibitory molecules. In the skin allograft, Tregs increased after low-dose IL-2 therapy. IL-2 induced a distinct molecular signature in the allograft with reduced cytotoxicity-associated genes (granzyme B and perforin). Two complications were observed during the trial: one rejection event and an episode of autoimmune hemolytic anemia. In summary, this initial experience demonstrated that low-dose IL-2 therapy was not only able to promote immune regulation in face transplant recipients but also highlighted challenges related to its narrow therapeutic window. More specific targeted Treg expansion strategies are needed to translate this approach to the clinic.
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a transplantace obličeje $7 D054445
- 650 _2
- $a rejekce štěpu $7 D006084
- 650 12
- $a interleukin-2 $x aplikace a dávkování $x imunologie $7 D007376
- 650 _2
- $a pilotní projekty $7 D010865
- 650 _2
- $a regulační T-lymfocyty $7 D050378
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a Research Support, N.I.H., Extramural $7 D052061
- 655 _2
- $a práce podpořená grantem $7 D013485
- 655 _2
- $a Research Support, U.S. Gov't, Non-P.H.S. $7 D013486
- 700 1_
- $a Borges, Thiago J $u Transplant Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Win, Thet Su $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Abarzua, Phammela $u Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Tasigiorgos, Sotirios $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Kollar, Branislav $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Medical Faculty of the University of Freiburg, Freiburg, Germany
- 700 1_
- $a Barrera, Victor $u Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Maryland, USA
- 700 1_
- $a Ho Sui, Shannan $u Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Maryland, USA
- 700 1_
- $a Teague, Jessica E $u Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Bueno, Ericka $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Clark, Rachael A $u Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Lian, Christine G $u Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Murphy, George F $u Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA
- 700 1_
- $a Pomahac, Bohdan $u Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Department of Surgery, Division of Plastic and Reconstructive Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, Connecticut, USA. Electronic address: bohdan.pomahac@yale.edu
- 700 1_
- $a Riella, Leonardo V $u Transplant Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Maryland, USA. Electronic address: lriella@mgh.harvard.edu
- 773 0_
- $w MED00006447 $t American journal of transplantation $x 1600-6143 $g Roč. 23, č. 4 (2023), s. 549-558
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/36740193 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20240220 $b ABA008
- 991 __
- $a 20240509113211 $b ABA008
- 999 __
- $a ok $b bmc $g 2088855 $s 1212939
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2023 $b 23 $c 4 $d 549-558 $e 20230204 $i 1600-6143 $m American journal of transplantation $n Am J Transplant $x MED00006447
- GRA __
- $a K08 DK120868 $p NIDDK NIH HHS $2 United States
- GRA __
- $a R01 AI143887 $p NIAID NIH HHS $2 United States
- GRA __
- $a T32 DK007527 $p NIDDK NIH HHS $2 United States
- GRA __
- $a UL1 RR025758 $p NCRR NIH HHS $2 United States
- LZP __
- $a Pubmed-20240220
