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

被引：9

作者：

Borges, Thiago J. ^{[1
,2
]}

Abarzua, Phammela ^{[3
]}

Gassen, Rodrigo B. ^{[2
]}

Kollar, Branislav ^{[4
,5
]}

Lima-Filho, Mauricio ^{[1
]}

Aoyama, Bruno T. ^{[1
]}

Gluhova, Diana ^{[6
]}

Clark, Rachael A. ^{[7
]}

Islam, Sabina A. ^{[8
]}

Pomahac, Bohdan ^{[4
]}

Murphy, George F. ^{[3
]}

Lian, Christine G. ^{[3
]}

Talbot, Simon G. ^{[4
]}

Riella, Leonardo, V ^{[1
,2
,9
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Schuster Family Transplantat Res Ctr, Renal Div, Boston, MA 02115 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Transplantat Sci, Dept Surg, Boston, MA 02129 USA

[3] Brigham & Womens Hosp, Dept Pathol, Program Dermatopathol, Boston, MA 02115 USA

[4] Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA

[5] Univ Freiburg, Med Ctr, Fac Med, Dept Plast & Hand Surg, D-79106 Freiburg, Germany

[6] Massachusetts Gen Hosp Site, DF HCC Specialized Histopathol Core, Boston, MA 02129 USA

[7] Harvard Med Sch, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA

[8] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02129 USA

[9] Harvard Med Sch, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA

来源：

CELL REPORTS MEDICINE | 2022年 / 3卷 / 03期

关键词：

ATOPIC-DERMATITIS; SKIN; EXPRESSION; SUBSETS; PATHWAY; KIDNEY; CC-CHEMOKINE-LIGAND-18; BIOMARKER; RESIDENT; MODEL;

D O I：

10.1016/j.xcrm.2022.100559

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：18

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