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Updated: Aug 23, 2025
Single-cell Gene Expression Using Multiplex RT-qPCR to Characterize Heterogeneity of Rare Lymphoid Populations
Published on: January 19, 2017
Single-Cell Heterogeneity of the Liver-Infiltrating Lymphocytes in Individuals with Chronic Echinococcus
Tiemin Jiang1, Wujianan Sun2, Tuerganaili Aji3
1State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical Universitygrid.412631.3, Urumqi, Xinjiang, China.
Insights
Human alveolar echinococcosis (AE) involves a complex immune microenvironment. This study reveals specific T cell subsets and innate lymphoid cells in AE lesions contribute to immune suppression and tumor metastasis, offering potential therapeutic targets.
Area of Science:
- Immunology
- Oncology
- Parasitology
Background:
- Human alveolar echinococcosis (AE) is a liver disease forming tumor-like lesions.
- The immune cell composition and function within AE lesions remain poorly understood.
- AE creates an immunosuppressive microenvironment that may promote disease progression.
Purpose of the Study:
- To comprehensively profile immune cells infiltrating AE liver lesions.
- To identify specific lymphocyte subsets and their roles in the AE microenvironment.
- To uncover potential diagnostic markers and therapeutic targets for AE.
Main Methods:
- Single-cell RNA and T-cell receptor (TCR) sequencing of 83,921 lymphocytes from AE patients.
- Analysis of cells from peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue.
- Identification and characterization of distinct immune cell clusters and their transcriptomic profiles.
Main Results:
- Distinct immune cell distributions and transcriptomes were observed between liver and peripheral blood.
- Exhausted CD8+ T cells and group 2 innate lymphoid cells (ILC2s) were enriched in PL tissue, associated with metastasis and immune suppression.
- CD8+ MAIT cells, Th17 cells, and induced regulatory T cells (iTregs) were enriched in PL tissue, with gene expression linked to invasion and immunosuppression.
- Upregulation of exhaustion markers (TIGIT, PD-1, CTLA4) on Tregs and close interactions between CD8+ T cells and iTregs/Th17 cells, involving immunosuppressive genes like PDCD1-FAM3C.
Conclusions:
- The study provides a detailed atlas of the immune microenvironment in human AE liver lesions.
- Specific immune cell subsets, including exhausted CD8+ T cells, ILC2s, MAIT cells, Th17 cells, and iTregs, play critical roles in AE pathogenesis.
- These findings offer potential molecular signatures for AE diagnosis and novel targets for immunotherapies.
Abstract:
Human alveolar echinococcosis (AE) is a tumor-like disease predominantly located in the liver. The cellular composition and heterogeneity of the lesion-infiltrating lymphocytes which produce an "immunosuppressive" microenvironment are poorly understood. Here, we profiled 83,921 CD45+ lymphocytes isolated from the peripheral blood (PB), perilesion (PL), and adjacent normal (AN) liver tissue of four advanced-stage AE patients using single-cell RNA and T-cell receptor (TCR) sequencing technology. We identified 23 large clusters, and the distributions and transcriptomes of these cell clusters in the liver and periphery were different. The cellular proportions of exhausted CD8+ T cells and group 2 innate lymphoid cells (ILC2s) were notably higher in PL tissue, and the expression features of these cell subsets were related to neoplasm metastasis and immune response suppression. In the 5 CD8+ T-cell populations, only CD8+ mucosa-associated invariant T (MAIT) cells were enriched in PL samples and the TRAV1-2_TRAJ33_TRAC TCR was clonally expanded. In the 11 subsets of CD4+ T cells, Th17 cells and induced regulatory T cells (iTregs) were preferentially enriched in PL samples, and their highly expressed genes were related to cell invasion, tumor metastasis, and inhibition of the inflammatory immune response. Exhaustion-specific genes (TIGIT, PD-1, and CTLA4) were upregulated in Tregs. Interestingly, there was a close contact between CD8+ T cells and iTregs or Th17 cells, especially for genes related to immunosuppression, such as PDCD1-FAM3C, which were highly expressed in PL tissue. This transcriptional data set provides valuable insights and a rich resource for deeply understanding the immune microenvironment in AE, which could provide potential target signatures for AE diagnosis and immunotherapies.
