T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation.
T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation.
复制标题
DOI：
10.1016/j.xcrm.2022.100559
复制
发表时间：
2022-03-15
影响因子：
14.3
通讯作者：
Riella, Leonardo, V
中科院分区：
文献类型：
--
作者：
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
肢体移植是一个改变截肢者生活的过程。然而，肢体接受者的排斥率比实体器官移植接受者高6倍，部分原因与皮肤的免疫原性更强有关。在这里，我们报告了一个详细的免疫学和分子特征的个人谁经历了双边肢体移植在我们的机构。循环Th17细胞在肢体移植受者中随时间增加。皮肤活检中770个基因的分子表征揭示了T细胞效应免疫分子和趋化因子的上调，特别是CCL18。皮肤抗原呈递细胞主要表达与CCR8受体结合的趋化因子CCL18。在人源化皮肤移植模型中，CCL18治疗将更多的同种异体T细胞募集到皮肤异种移植物中，导致加速移植排斥的迹象。阻断CCR8可显著减少CCL18诱导的同种异体T细胞浸润。我们的研究结果表明，靶向CCL18：CCR8通路可能是移植中一种有前途的免疫抑制方法。与天然皮肤相比，稳定移植物中T细胞浸润增加趋化因子CCL18在肢体移植排斥反应期间上调CCL18向皮肤募集更多的同种异体T细胞，并导致加速异种移植物损失CCR8阻断阻止CCL18介导的T细胞浸润Borges et al.提供了一个全面的肢体移植受体的免疫特征，证明趋化因子CCL18是排斥反应期间的主导信号。局部CCL18介导致病性同种异体T细胞向移植物中的募集，这被CCR8阻断所废除。靶向CCL18：CCR8通路是移植中有前途的补充免疫抑制方法。
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. Increased T cell infiltration in the stable graft compared with native skin The chemokine CCL18 is upregulated during rejection in limb transplantation CCL18 recruits more allo-T cells to the skin and leads to accelerated xenograft loss CCR8 blockade halts CCL18-mediated T cell infiltration Borges et al. provide a comprehensive immune characterization of limb transplant recipients, demonstrating that the chemokine CCL18 is a dominant signal during rejection. Local CCL18 mediates recruitment of pathogenic allo-T cells into grafts, which is abrogated by CCR8 blockade. Targeting the CCL18:CCR8 pathway is a promising complementary immunosuppressive approach in transplantation.
登录
查看更多内容
DOI：
10.1084/jem.20130240
发表时间：
2013-09-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Islam SA;Ling MF;Leung J;Shreffler WG;Luster AD
通讯作者：
Luster AD
患有慢性同种异体功能障碍的肾脏移植受者中Th17细胞表型的增加。
影响因子：
3.7
作者：
Chung BH;Kim KW;Kim BM;Doh KC;Cho ML;Yang CW
通讯作者：
Yang CW
影响因子：
28.1
作者：
Kaminski, Michael M.;Alcantar, Miguel A.;Collins, James J.
通讯作者：
Collins, James J.
影响因子：
14.9
作者：
Metsalu T;Vilo J
通讯作者：
Vilo J
DOI：
10.1111/ajt.12426
发表时间：
2013-10
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Hricik DE;Nickerson P;Formica RN;Poggio ED;Rush D;Newell KA;Goebel J;Gibson IW;Fairchild RL;Riggs M;Spain K;Ikle D;Bridges ND;Heeger PS;CTOT-01 consortium
通讯作者：
CTOT-01 consortium