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T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation

Limb transplantation is a life-changing procedure for amputees. However, limb recipients have a 6-fold greater rejection rate than solid organ transplant recipients, related in part to greater immunogenicity of the skin. Here, we report a detailed immunological and molecular characterization of indi...

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Autores principales: Borges, Thiago J., Abarzua, Phammela, Gassen, Rodrigo B., Kollar, Branislav, Lima-Filho, Mauricio, Aoyama, Bruno T., Gluhova, Diana, Clark, Rachael A., Islam, Sabina A., Pomahac, Bohdan, Murphy, George F., Lian, Christine G., Talbot, Simon G., Riella, Leonardo V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040185/
https://www.ncbi.nlm.nih.gov/pubmed/35492875
http://dx.doi.org/10.1016/j.xcrm.2022.100559
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author Borges, Thiago J.
Abarzua, Phammela
Gassen, Rodrigo B.
Kollar, Branislav
Lima-Filho, Mauricio
Aoyama, Bruno T.
Gluhova, Diana
Clark, Rachael A.
Islam, Sabina A.
Pomahac, Bohdan
Murphy, George F.
Lian, Christine G.
Talbot, Simon G.
Riella, Leonardo V.
author_facet Borges, Thiago J.
Abarzua, Phammela
Gassen, Rodrigo B.
Kollar, Branislav
Lima-Filho, Mauricio
Aoyama, Bruno T.
Gluhova, Diana
Clark, Rachael A.
Islam, Sabina A.
Pomahac, Bohdan
Murphy, George F.
Lian, Christine G.
Talbot, Simon G.
Riella, Leonardo V.
author_sort Borges, Thiago J.
collection PubMed
description Limb transplantation is a life-changing procedure for amputees. However, limb recipients have a 6-fold greater rejection rate than solid organ transplant recipients, related in part to greater immunogenicity of the skin. Here, we report a detailed immunological and molecular characterization of individuals who underwent bilateral limb transplantation at our institution. Circulating Th17 cells are increased in limb transplant recipients over time. Molecular characterization of 770 genes in skin biopsies reveals upregulation of T cell effector immune molecules and chemokines, particularly CCL18. Skin antigen-presenting cells primarily express the chemokine CCL18, which binds to the CCR8 receptor. CCL18 treatment recruits more allo-T cells to the skin xenograft in a humanized skin transplantation model, leading to signs of accelerated graft rejection. Blockade of CCR8 remarkedly decreases CCL18-induced allo-T cell infiltration. Our results suggest that targeting the CCL18:CCR8 pathway could be a promising immunosuppressive approach in transplantation.
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spelling pubmed-90401852022-04-27 T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation Borges, Thiago J. Abarzua, Phammela Gassen, Rodrigo B. Kollar, Branislav Lima-Filho, Mauricio Aoyama, Bruno T. Gluhova, Diana Clark, Rachael A. Islam, Sabina A. Pomahac, Bohdan Murphy, George F. Lian, Christine G. Talbot, Simon G. Riella, Leonardo V. Cell Rep Med Article Limb transplantation is a life-changing procedure for amputees. However, limb recipients have a 6-fold greater rejection rate than solid organ transplant recipients, related in part to greater immunogenicity of the skin. Here, we report a detailed immunological and molecular characterization of individuals who underwent bilateral limb transplantation at our institution. Circulating Th17 cells are increased in limb transplant recipients over time. Molecular characterization of 770 genes in skin biopsies reveals upregulation of T cell effector immune molecules and chemokines, particularly CCL18. Skin antigen-presenting cells primarily express the chemokine CCL18, which binds to the CCR8 receptor. CCL18 treatment recruits more allo-T cells to the skin xenograft in a humanized skin transplantation model, leading to signs of accelerated graft rejection. Blockade of CCR8 remarkedly decreases CCL18-induced allo-T cell infiltration. Our results suggest that targeting the CCL18:CCR8 pathway could be a promising immunosuppressive approach in transplantation. Elsevier 2022-03-15 /pmc/articles/PMC9040185/ /pubmed/35492875 http://dx.doi.org/10.1016/j.xcrm.2022.100559 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Borges, Thiago J.
Abarzua, Phammela
Gassen, Rodrigo B.
Kollar, Branislav
Lima-Filho, Mauricio
Aoyama, Bruno T.
Gluhova, Diana
Clark, Rachael A.
Islam, Sabina A.
Pomahac, Bohdan
Murphy, George F.
Lian, Christine G.
Talbot, Simon G.
Riella, Leonardo V.
T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
title T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
title_full T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
title_fullStr T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
title_full_unstemmed T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
title_short T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
title_sort t cell-attracting ccl18 chemokine is a dominant rejection signal during limb transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040185/
https://www.ncbi.nlm.nih.gov/pubmed/35492875
http://dx.doi.org/10.1016/j.xcrm.2022.100559
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