Nanoparticle-mediated targeting of autoantigen peptide to cross-presenting liver sinusoidal endothelial cells protects from CD8 T-cell-driven autoimmune cholangitis
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Nanoparticle-mediated targeting of autoantigen peptide to cross-presenting liver sinusoidal endothelial cells protects from CD8 T-cell-driven autoimmune cholangitis. / Carambia, Antonella; Gottwick, Cornelia; Schwinge, Dorothee; Stein, Stephanie; Digigow, Reinaldo; Şeleci, Muharrem; Mungalpara, Disha; Heine, Markus; Schuran, Fenja A; Corban, Carlotta; Lohse, Ansgar W; Schramm, Christoph; Heeren, Joerg; Herkel, Johannes.
in: IMMUNOLOGY, Jahrgang 162, Nr. 4, 04.2021, S. 452-463.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Nanoparticle-mediated targeting of autoantigen peptide to cross-presenting liver sinusoidal endothelial cells protects from CD8 T-cell-driven autoimmune cholangitis
AU - Carambia, Antonella
AU - Gottwick, Cornelia
AU - Schwinge, Dorothee
AU - Stein, Stephanie
AU - Digigow, Reinaldo
AU - Şeleci, Muharrem
AU - Mungalpara, Disha
AU - Heine, Markus
AU - Schuran, Fenja A
AU - Corban, Carlotta
AU - Lohse, Ansgar W
AU - Schramm, Christoph
AU - Heeren, Joerg
AU - Herkel, Johannes
N1 - © 2021 The Authors. Immunology published by John Wiley & Sons Ltd.
PY - 2021/4
Y1 - 2021/4
N2 - Autoimmune diseases are caused by adaptive immune responses to self-antigens. The development of antigen-specific therapies that suppress disease-related, but not unrelated immune responses in general, is an important goal of biomedical research. We have previously shown that delivery of myelin peptides to liver sinusoidal endothelial cells (LSECs) using LSEC-targeting nanoparticles provides effective protection from CD4 T-cell-driven autoimmune encephalomyelitis. Here, we investigated whether this methodology might also serve antigen-specific treatment of a CD8 T-cell-driven autoimmune disease. As a model for CD8 T-cell-mediated autoimmunity, we used OT-1 T-cell-driven cholangitis in K14-OVAp mice expressing the cognate MHC I-restricted SIINFEKL peptide in cholangiocytes. To study whether peptide delivery to LSECs could modulate cholangitis, SIINFEKL peptide-conjugated nanoparticles were administered intravenously one day before transfer of OT-1 T cells; five days after cell transfer, liver pathology and hepatic infiltrates were analysed. SIINFEKL peptide-conjugated nanoparticles were rapidly taken up by LSECs in vivo, which effectively cross-presented the delivered peptide on MHC I molecules. Intriguingly, K14-OVAp mice receiving SIINFEKL-loaded nanoparticles manifested significantly reduced liver damage compared with vehicle-treated K14-OVAp mice. Mechanistically, treatment with LSEC-targeting SIINFEKL-loaded nanoparticles significantly reduced the number of liver-infiltrating OT-1 T cells, which up-regulated expression of the co-inhibitory receptor PD-1 and down-regulated cytotoxic effector function and inflammatory cytokine production. These findings show that tolerogenic LSECs can effectively internalize circulating nanoparticles and cross-present nanoparticle-bound peptides on MHC I molecules. Therefore, nanoparticle-mediated autoantigen peptide delivery to LSECs might serve the antigen-specific treatment of CD8 T-cell-driven autoimmune disease.
AB - Autoimmune diseases are caused by adaptive immune responses to self-antigens. The development of antigen-specific therapies that suppress disease-related, but not unrelated immune responses in general, is an important goal of biomedical research. We have previously shown that delivery of myelin peptides to liver sinusoidal endothelial cells (LSECs) using LSEC-targeting nanoparticles provides effective protection from CD4 T-cell-driven autoimmune encephalomyelitis. Here, we investigated whether this methodology might also serve antigen-specific treatment of a CD8 T-cell-driven autoimmune disease. As a model for CD8 T-cell-mediated autoimmunity, we used OT-1 T-cell-driven cholangitis in K14-OVAp mice expressing the cognate MHC I-restricted SIINFEKL peptide in cholangiocytes. To study whether peptide delivery to LSECs could modulate cholangitis, SIINFEKL peptide-conjugated nanoparticles were administered intravenously one day before transfer of OT-1 T cells; five days after cell transfer, liver pathology and hepatic infiltrates were analysed. SIINFEKL peptide-conjugated nanoparticles were rapidly taken up by LSECs in vivo, which effectively cross-presented the delivered peptide on MHC I molecules. Intriguingly, K14-OVAp mice receiving SIINFEKL-loaded nanoparticles manifested significantly reduced liver damage compared with vehicle-treated K14-OVAp mice. Mechanistically, treatment with LSEC-targeting SIINFEKL-loaded nanoparticles significantly reduced the number of liver-infiltrating OT-1 T cells, which up-regulated expression of the co-inhibitory receptor PD-1 and down-regulated cytotoxic effector function and inflammatory cytokine production. These findings show that tolerogenic LSECs can effectively internalize circulating nanoparticles and cross-present nanoparticle-bound peptides on MHC I molecules. Therefore, nanoparticle-mediated autoantigen peptide delivery to LSECs might serve the antigen-specific treatment of CD8 T-cell-driven autoimmune disease.
U2 - 10.1111/imm.13298
DO - 10.1111/imm.13298
M3 - SCORING: Journal article
C2 - 33346377
VL - 162
SP - 452
EP - 463
JO - IMMUNOLOGY
JF - IMMUNOLOGY
SN - 0019-2805
IS - 4
ER -