Dataset Information

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4⁺ T Lymphocytes and a Landscape of Immune Cells in Primary Sjogren's Syndrome.

ABSTRACT:

Objective

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, and its pathogenetic mechanism is far from being understood. In this study, we aimed to explore the cellular and molecular mechanisms that lead to pathogenesis of this disease.

Methods

We applied single-cell RNA sequencing (scRNA-seq) to 57,288 peripheral blood mononuclear cells (PBMCs) from five patients with pSS and five healthy controls. The immune cell subsets and susceptibility genes involved in the pathogenesis of pSS were analyzed. Flow cytometry was preformed to verify the result of scRNA-seq.

Results

We identified two subpopulations significantly expand in pSS patients. The one highly expressing cytotoxicity genes is named as CD4⁺ CTLs cytotoxic T lymphocyte, and another highly expressing T cell receptor (TCR) variable gene is named as CD4⁺ TRAV13-2+ T cell. Flow cytometry results showed the percentages of CD4⁺ CTLs, which were profiled with CD4⁺ and GZMB⁺ staining; the total T cells of 10 patients with pSS were significantly higher than those of 10 healthy controls (P= 0.008). The expression level of IL-1? in macrophages, TCL1A in B cells, as well as interferon (IFN) response genes in most cell subsets was upregulated in the patients with pSS. Susceptibility genes including HLA-DRB5, CTLA4, and AQP3 were highly expressed in patients with pSS.

Conclusions

Our data revealed disease-specific immune cell subsets and provided some potential new targets of pSS. Specific expansion of CD4⁺ CTLs may be involved in the pathogenesis of pSS, which might give valuable insights for therapeutic interventions of pSS.

SUBMITTER: Hong X

PROVIDER: S-EPMC7884617 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4<sup>+</sup> T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren's Syndrome.

Hong Xiaoping X Meng Shuhui S Tang Donge D Wang Tingting T Ding Liping L Yu Haiyan H Li Heng H Liu Dongzhou D Dai Yong Y Yang Min M

Frontiers in immunology 20210202

<h4>Objective</h4>Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, and its pathogenetic mechanism is far from being understood. In this study, we aimed to explore the cellular and molecular mechanisms that lead to pathogenesis of this disease.<h4>Methods</h4>We applied single-cell RNA sequencing (scRNA-seq) to 57,288 peripheral blood mononuclear cells (PBMCs) from five patients with pSS and five healthy controls. The immune cell subsets and susceptibility genes involved in the ...[more]

PMID: 33603736

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Project description:BackgroundMismatch repair proficient colorectal cancer (pMMR CRC) lacks effective treatments and has a poor prognosis, which can be attributed to the complexity of tumor microenvironment. The coordinated function of immune cells is vital to anti-tumor immunity. However, the spatial characteristics of immune cells in the pMMR CRC immune microenvironment and their relationship with clinical prognosis are not fully understood. Meanwhile, the immune modulatory effect of neoadjuvant chemotherapy (NCT), which is the first-line treatment of pMMR CRC, needs further investigation. Therefore, this study aims to explore the spatial dynamics of immune cells and its prognostic value in pMMR CRC.MethodsWe analyzed the various immune cells in formalin-fixed, paraffin-embedded tumor tissues which were collected from 77 patients with stage II/III of pMMR CRC, including 39 non-NCT treated and 38 NCT treated patients. We used the optimized multiplex immunohistochemistry (mIHC) to identify and quantify the density, type and location of immune cells in pMMR CRC. Multivariate survival analysis was performed to assess the relationship of immune profiles and clinical prognosis of pMMR CRC patients.ResultsThe densities of most T cell subsets, B cells and macrophages were higher in the central region of the pMMR CRC than in the invasion margin. Tumor infiltrating lymphocytes (TILs), especially the infiltration of CD4+ GzmB+ T cells in the central region of the tumor was identified to be positively correlated with the prognosis of the patients. Multivariate analysis confirmed that CD4+ GzmB+ T cells population was an independent predictor of disease-free survival (DFS) in non-NCT group. Meanwhile, NCT enhanced the infiltration of CD4+ GzmB+ T cells in the central region of the pMMR CRC, which was also identified as an independent protective factor of overall survival (OS) and DFS in NCT group.ConclusionWe demonstrated that the level of CD4+ GzmB+ T cells located in the center of tumor could provide great prognostic value for pMMR CRC patients. And the application of neoadjuvant chemotherapy further improves the infiltration of CD4+ GzmB+ T cells in the central compartment. Further studies into the application of CD4+ GzmB+ T cells in tumor immunotherapy are needed.

Project description:PurposeImmune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8+ lymphocytes in a wide range of different cancer types and subtypes.MethodsThe density of CD8+ lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides.ResultsWe found that the median CD8+ lymphocyte counts ranged from 6 cells/mm2 in pleomorphic adenoma up to 1573 cells/mm2 in Hodgkin's lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin's lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm2) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved.ConclusionThese data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

Dataset Information

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4⁺ T Lymphocytes and a Landscape of Immune Cells in Primary Sjogren's Syndrome.

Objective

Methods

Results

Conclusions

Publications

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4<sup>+</sup> T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren's Syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjogren's Syndrome.

Objective

Methods

Results

Conclusions

Publications

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4<sup>+</sup> T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren's Syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4⁺ T Lymphocytes and a Landscape of Immune Cells in Primary Sjogren's Syndrome.