Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice
Standard
Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. / Carambia, Antonella; Freund, Barbara; Schwinge, Dorothee; Bruns, Oliver T; Salmen, Sunhild C; Ittrich, Harald; Reimer, Rudolph; Heine, Markus; Huber, Samuel; Waurisch, Christian; Eychmüller, Alexander; Wraith, David C; Korn, Thomas; Nielsen, Peter; Weller, Horst; Schramm, Christoph; Lüth, Stefan; Lohse, Ansgar W; Heeren, Joerg; Herkel, Johannes.
in: J HEPATOL, Jahrgang 62, Nr. 6, 21.01.2015, S. 1349-1356.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice
AU - Carambia, Antonella
AU - Freund, Barbara
AU - Schwinge, Dorothee
AU - Bruns, Oliver T
AU - Salmen, Sunhild C
AU - Ittrich, Harald
AU - Reimer, Rudolph
AU - Heine, Markus
AU - Huber, Samuel
AU - Waurisch, Christian
AU - Eychmüller, Alexander
AU - Wraith, David C
AU - Korn, Thomas
AU - Nielsen, Peter
AU - Weller, Horst
AU - Schramm, Christoph
AU - Lüth, Stefan
AU - Lohse, Ansgar W
AU - Heeren, Joerg
AU - Herkel, Johannes
N1 - Copyright © 2015. Published by Elsevier B.V.
PY - 2015/1/21
Y1 - 2015/1/21
N2 - BACKGROUND & AIMS: It is well known that the liver can induce immune tolerance, yet this knowledge could thus far not be translated into effective treatments for autoimmune diseases. We have previously shown that liver sinusoidal endothelial cells (LSECs) could substantially contribute to hepatic tolerance through their ability to induce CD4+ Foxp3+ regulatory T cells (Tregs). Here, we explored whether the Treg-inducing potential of LSECs could be harnessed for the treatment of autoimmune disease.METHODS: We engineered a polymeric nanoparticle (NP) carrier for the selective delivery of autoantigen peptides to LSECs in vivo. In the well-characterized autoimmune disease model of experimental autoimmune encephalomyelitis (EAE), we investigated whether administration of LSEC-targeting autoantigen peptide-loaded NPs could protect mice from autoimmune disease.RESULTS: We demonstrate that NP-based autoantigen delivery to LSECs could completely and lastingly prevent the onset of clinical EAE. More importantly, in a therapeutic approach, mice with already established EAE improved rapidly and substantially following administration of a single dose of autoantigen peptide-loaded NPs, whereas the control group deteriorated. Treatment efficacy seemed to depend on Tregs, because the Treg frequencies in the spleens of mice treated with autoantigen peptide-loaded NPs were significantly higher than those in vehicle-treated mice. Moreover, NP-mediated disease control was abrogated after Treg-depletion by repeated administration of Treg-depleting antibody.CONCLUSION: Our findings provide proof-of-principle that the selective delivery of autoantigen peptides to LSECs by nanoparticles can induce antigen-specific Tregs and enable effective treatment of autoimmune disease. These findings underscore the importance of Treg-induction by LSECs for immune tolerance.
AB - BACKGROUND & AIMS: It is well known that the liver can induce immune tolerance, yet this knowledge could thus far not be translated into effective treatments for autoimmune diseases. We have previously shown that liver sinusoidal endothelial cells (LSECs) could substantially contribute to hepatic tolerance through their ability to induce CD4+ Foxp3+ regulatory T cells (Tregs). Here, we explored whether the Treg-inducing potential of LSECs could be harnessed for the treatment of autoimmune disease.METHODS: We engineered a polymeric nanoparticle (NP) carrier for the selective delivery of autoantigen peptides to LSECs in vivo. In the well-characterized autoimmune disease model of experimental autoimmune encephalomyelitis (EAE), we investigated whether administration of LSEC-targeting autoantigen peptide-loaded NPs could protect mice from autoimmune disease.RESULTS: We demonstrate that NP-based autoantigen delivery to LSECs could completely and lastingly prevent the onset of clinical EAE. More importantly, in a therapeutic approach, mice with already established EAE improved rapidly and substantially following administration of a single dose of autoantigen peptide-loaded NPs, whereas the control group deteriorated. Treatment efficacy seemed to depend on Tregs, because the Treg frequencies in the spleens of mice treated with autoantigen peptide-loaded NPs were significantly higher than those in vehicle-treated mice. Moreover, NP-mediated disease control was abrogated after Treg-depletion by repeated administration of Treg-depleting antibody.CONCLUSION: Our findings provide proof-of-principle that the selective delivery of autoantigen peptides to LSECs by nanoparticles can induce antigen-specific Tregs and enable effective treatment of autoimmune disease. These findings underscore the importance of Treg-induction by LSECs for immune tolerance.
U2 - 10.1016/j.jhep.2015.01.006
DO - 10.1016/j.jhep.2015.01.006
M3 - SCORING: Journal article
C2 - 25617499
VL - 62
SP - 1349
EP - 1356
JO - J HEPATOL
JF - J HEPATOL
SN - 0168-8278
IS - 6
ER -