Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice

Antonella Carambia; Barbara Freund; Dorothee Schwinge; Oliver T Bruns; Sunhild C Salmen; Harald Ittrich; Rudolph Reimer; Markus Heine; Samuel Huber; Christian Waurisch; Alexander Eychmüller; David C Wraith; Thomas Korn; Peter Nielsen; Horst Weller; Christoph Schramm; Stefan Lüth; Ansgar W Lohse; Joerg Heeren; Johannes Herkel

doi:10.1016/j.jhep.2015.01.006

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, Vol. 62, No. 6, 21.01.2015, p. 1349-1356.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Carambia, A, Freund, B, Schwinge, D, Bruns, OT, Salmen, SC, Ittrich, H, Reimer, R, Heine, M , Huber, S, Waurisch, C, Eychmüller, A, Wraith, DC, Korn, T, Nielsen, P, Weller, H, Schramm, C, Lüth, S, Lohse, AW , Heeren, J & Herkel, J 2015, 'Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice', J HEPATOL, vol. 62, no. 6, pp. 1349-1356. https://doi.org/10.1016/j.jhep.2015.01.006

APA

Carambia, A., Freund, B., Schwinge, D., Bruns, O. T., Salmen, S. C., Ittrich, H., Reimer, R., Heine, M., Huber, S., Waurisch, C., Eychmüller, A., Wraith, D. C., Korn, T., Nielsen, P., Weller, H., Schramm, C., Lüth, S., Lohse, A. W., Heeren, J., & Herkel, J. (2015). Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. J HEPATOL, 62(6), 1349-1356. https://doi.org/10.1016/j.jhep.2015.01.006

Vancouver

Carambia A, Freund B, Schwinge D, Bruns OT, Salmen SC, Ittrich H et al. Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. J HEPATOL. 2015 Jan 21;62(6):1349-1356. https://doi.org/10.1016/j.jhep.2015.01.006

Bibtex

@article{52d5dc94b2ab428294c24618a8a5d745,

title = "Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice",

abstract = "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.",

author = "Antonella Carambia and Barbara Freund and Dorothee Schwinge and Bruns, {Oliver T} and Salmen, {Sunhild C} and Harald Ittrich and Rudolph Reimer and Markus Heine and Samuel Huber and Christian Waurisch and Alexander Eychm{\"u}ller and Wraith, {David C} and Thomas Korn and Peter Nielsen and Horst Weller and Christoph Schramm and Stefan L{\"u}th and Lohse, {Ansgar W} and Joerg Heeren and Johannes Herkel",

note = "Copyright {\textcopyright} 2015. Published by Elsevier B.V.",

year = "2015",

month = jan,

day = "21",

doi = "10.1016/j.jhep.2015.01.006",

language = "English",

volume = "62",

pages = "1349--1356",

journal = "J HEPATOL",

issn = "0168-8278",

publisher = "Elsevier",

number = "6",

}

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

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 -