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T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
TJ. Borges, P. Abarzua, RB. Gassen, B. Kollar, M. Lima-Filho, BT. Aoyama, D. Gluhova, RA. Clark, SA. Islam, B. Pomahac, GF. Murphy, CG. Lian, SG. Talbot, LV. Riella
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
Grantová podpora
R01 AI121248
NIAID NIH HHS - United States
R56 AI101348
NIAID NIH HHS - United States
NLK
Directory of Open Access Journals
od 2020
PubMed Central
od 2020
Elsevier Open Access Journals
od 2020-04-21
ROAD: Directory of Open Access Scholarly Resources
od 2020
- MeSH
- chemokiny CC genetika MeSH
- chemokiny * MeSH
- imunosupresiva MeSH
- kůže MeSH
- lidé MeSH
- transplantace kůže * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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.
Department of Dermatology Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USA
DF HCC Specialized Histopathology Core Massachusetts General Hospital Site Boston MA 02129 USA
Division of Nephrology Massachusetts General Hospital Harvard Medical School Boston MA 02114 USA
Program in Dermatopathology Department of Pathology Brigham and Women's Hospital Boston MA 02115 USA
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- $a 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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