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Single-cell RNA sequencing revealed the role of the Th17 pathway in the development of anti- human leukocyte antigen antibodies in a highly sensitized mouse model.
Lee, Hanbi; Shin, Yoo-Jin; Fang, Xianying; Cui, Sheng; Lim, Sun Woo; Lee, Seon-Yeong; Eum, Sang Hun; Min, Ji-Won; Hong, Chang-Won; Lee, Hae-Ock; Cho, Mi-La; Oh, Eun-Jee; Yang, Chul Woo; Chung, Byung Ha.
Afiliación
  • Lee H; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Shin YJ; Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Fang X; Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Cui S; Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Lim SW; Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Lee SY; Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Eum SH; The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Min JW; Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Lee HO; Transplant Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
  • Cho ML; Division of Nephrology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea.
  • Oh EJ; Department of Physiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
  • Yang CW; Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.
  • Chung BH; The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Kidney Res Clin Pract ; 2024 Jun 13.
Article en En | MEDLINE | ID: mdl-38934039
ABSTRACT

Background:

The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse.

Methods:

For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them.

Results:

We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN.

Conclusion:

Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Kidney Res Clin Pract Año: 2024 Tipo del documento: Article Pais de publicación:
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Kidney Res Clin Pract Año: 2024 Tipo del documento: Article Pais de publicación: