Autoimmune-shared immune states converge in a CXCL12-CXCR4 fibroblast-immune niche in chronic antibody-mediated rejection.
13 affiliations
- 1Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
- 2Sichuan Clinical Research Center for Laboratory Medicine, Chengdu, China.
- 3Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
- 4State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
- 5Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China.
- 6Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
- 7Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China. [email protected].
- 8Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China. [email protected].
- 9State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [email protected].
- 10Institute of General Surgery, West China Hospital, Sichuan University, Chengdu, China. [email protected].
- 11Tianfu Jincheng Laboratory, Chengdu, China. [email protected].
- 12Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China. [email protected].
- 13Sichuan Clinical Research Center for Laboratory Medicine, Chengdu, China. [email protected].
Abstract
Chronic antibody-mediated rejection (CAMR) is a leading cause of late kidney allograft failure and shares features of chronic immune activation with systemic autoimmune diseases, but how circulating immune states connect to spatially organized graft injury and whether related immune features recur in autoimmune inflammation remain unclear. Here, we integrated single-cell profiles from peripheral blood and kidney graft samples from patients with CAMR or stable allograft function and healthy controls with independent transplant cohorts, bulk transcriptomic datasets, spectral flow cytometry, multiplex immunofluorescence, high-resolution spatial transcriptomics, and a large blood immune reference spanning autoimmune and inflammatory diseases. CAMR was associated with reproducible myeloid expansion and enrichment of SLC8A1⁺ monocytes/macrophages, ANK3⁺CD4⁺ memory T cells, ZEB2hi T cells, and CD16⁺ NK cells. These subsets showed migratory and tissue-interacting transcriptional features, including recurrent CXCR4 and ZEB2 expression, suggesting candidate immune states potentially linked to local graft immune organization. In graft tissue, CXCL12-expressing fibroblasts and CXCR4-expressing immune cells were increased in CAMR. High-resolution spatial transcriptomics localized this fibroblast-immune architecture to perivascular regions marked by endothelial activation and stromal remodeling and placed CAMR-associated immune states within adjacent immune-rich neighborhoods, supporting a CXCL12-CXCR4 axis that may be associated with local immune accumulation. Comparisons with large-scale blood immune reference data and spatial transcriptomic datasets from rheumatoid arthritis and systemic lupus erythematosus suggested partial recurrence of related immune states and fibroblast-immune organization. Together, this study links circulating CAMR immune remodeling to a spatially organized CXCL12-CXCR4 fibroblast-immune niche and suggests that elements of this niche recur across alloimmune and autoimmune inflammation.
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BibTeX
@article{xia2026autoimmuneshared,
title = {{Autoimmune-shared immune states converge in a CXCL12-CXCR4 fibroblast-immune niche in chronic antibody-mediated rejection.}},
author = {Xuyang Xia and Yangjuan Bai and Binqi Yang and Wei Mao and Hongyu Yang and Yamei Li and Yajiao He and Jing Wu and Bei Cai and Yu Fan and Haotian Yu and Yang Guo and Yanmei Liu and Xi Tang and Huayun Yan and Tao Zhou and Yiqi Deng and Wanchun Wu and Minyuan Cao and Yang Shu and Yun-Ying Shi and Heng Xu and Lanlan Wang},
journal = {Signal transduction and targeted therapy},
year = {2026},
month = nov,
doi = {10.1038/s41392-026-03017-4},
url = {https://europepmc.org/article/MED/42967934},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Autoimmune-shared immune states converge in a CXCL12-CXCR4 fibroblast-immune niche in chronic antibody-mediated rejection.
AU - Xuyang Xia
AU - Yangjuan Bai
AU - Binqi Yang
AU - Wei Mao
AU - Hongyu Yang
AU - Yamei Li
AU - Yajiao He
AU - Jing Wu
AU - Bei Cai
AU - Yu Fan
AU - Haotian Yu
AU - Yang Guo
AU - Yanmei Liu
AU - Xi Tang
AU - Huayun Yan
AU - Tao Zhou
AU - Yiqi Deng
AU - Wanchun Wu
AU - Minyuan Cao
AU - Yang Shu
AU - Yun-Ying Shi
AU - Heng Xu
AU - Lanlan Wang
PY - 2026
DA - 2026/11/02
JO - Signal transduction and targeted therapy
DO - 10.1038/s41392-026-03017-4
UR - https://europepmc.org/article/MED/42967934
AB - Chronic antibody-mediated rejection (CAMR) is a leading cause of late kidney allograft failure and shares features of chronic immune activation with systemic autoimmune diseases, but how circulating immune states connect to spatially organized graft injury and whether related immune features recur in autoimmune inflammation remain unclear. Here, we integrated single-cell profiles from peripheral blood and kidney graft samples from patients with CAMR or stable allograft function and healthy controls with independent transplant cohorts, bulk transcriptomic datasets, spectral flow cytometry, multiplex immunofluorescence, high-resolution spatial transcriptomics, and a large blood immune reference spanning autoimmune and inflammatory diseases. CAMR was associated with reproducible myeloid expansion and enrichment of SLC8A1⁺ monocytes/macrophages, ANK3⁺CD4⁺ memory T cells, ZEB2hi T cells, and CD16⁺ NK cells. These subsets showed migratory and tissue-interacting transcriptional features, including recurrent CXCR4 and ZEB2 expression, suggesting candidate immune states potentially linked to local graft immune organization. In graft tissue, CXCL12-expressing fibroblasts and CXCR4-expressing immune cells were increased in CAMR. High-resolution spatial transcriptomics localized this fibroblast-immune architecture to perivascular regions marked by endothelial activation and stromal remodeling and placed CAMR-associated immune states within adjacent immune-rich neighborhoods, supporting a CXCL12-CXCR4 axis that may be associated with local immune accumulation. Comparisons with large-scale blood immune reference data and spatial transcriptomic datasets from rheumatoid arthritis and systemic lupus erythematosus suggested partial recurrence of related immune states and fibroblast-immune organization. Together, this study links circulating CAMR immune remodeling to a spatially organized CXCL12-CXCR4 fibroblast-immune niche and suggests that elements of this niche recur across alloimmune and autoimmune inflammation.
SN - 2095-9907
SN - 2059-3635
ER -