scholarly journals Gene regulatory network of human GM-CSF secreting T helper cells

2019 ◽  
Author(s):  
Szabolcs Éliás ◽  
Angelika Schmidt ◽  
David Gomez-Cabrero ◽  
Jesper Tegnér
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Autoimmune Disease ◽  
T Helper Cells ◽  
Cd4 T Cells ◽  
T Helper ◽  
Human Autoimmune Disease ◽  
Gm Csf ◽  
Gene Regulatory ◽  
Memory Cd4 T Cells

ABSTRACTGM-CSF produced by autoreactive CD4 positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as Multiple Sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF positive CD4 T cells are unknown. In order to identify these regulators, we isolated human GM-CSF producing CD4 T cells from human peripheral blood by using a cytokine capture assay. We compared these cells to the corresponding GM-CSF negative fraction, and furthermore, we studied naïve CD4 T cells, memory CD4 T cells and bulk CD4 T cells from the same individuals as additional control cell populations. As a result, we provide a rich resource of integrated chromatin accessibility (ATAC-seq) and transcriptome (RNA-seq) data from these primary human CD4 T cell subsets, and we show that the identified signatures are associated with human autoimmune disease, especially Multiple Sclerosis. By combining information about mRNA expression, DNA accessibility and predicted transcription factor binding, we reconstructed directed gene regulatory networks connecting transcription factors to their targets, which comprise putative key regulators of human GM-CSF positive CD4 T cells as well as memory CD4 T cells. Our results suggest potential therapeutic targets to be investigated in the future in human autoimmune disease.

scholarly journals Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Szabolcs Éliás ◽  
Angelika Schmidt ◽  
David Gomez-Cabrero ◽  
Jesper Tegnér
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Autoimmune Diseases ◽  
T Helper Cells ◽  
Cd4 T Cells ◽  
T Helper ◽  
Gm Csf ◽  
Helper Cells ◽  
Gene Regulatory ◽  
Memory Cd4 T Cells

GM-CSF produced by autoreactive CD4-positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as multiple sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF-positive CD4 T cells are unknown. In order to identify these regulators, we isolated human GM-CSF-producing CD4 T cells from human peripheral blood by using a cytokine capture assay. We compared these cells to the corresponding GM-CSF-negative fraction, and furthermore, we studied naïve CD4 T cells, memory CD4 T cells, and bulk CD4 T cells from the same individuals as additional control cell populations. As a result, we provide a rich resource of integrated chromatin accessibility (ATAC-seq) and transcriptome (RNA-seq) data from these primary human CD4 T cell subsets and we show that the identified signatures are associated with human autoimmune diseases, especially multiple sclerosis. By combining information about mRNA expression, DNA accessibility, and predicted transcription factor binding, we reconstructed directed gene regulatory networks connecting transcription factors to their targets, which comprise putative key regulators of human GM-CSF-positive CD4 T cells as well as memory CD4 T cells. Our results suggest potential therapeutic targets to be investigated in the future in human autoimmune disease.

Virus-Specific CD4+ T Cells Have Functional and Phenotypic Characteristics of Follicular T-Helper Cells in Patients With Acute and Chronic HCV Infections

2016 ◽  
Vol 150 (3) ◽  
pp. 696-706.e3 ◽  
Author(s):  
Bijan Raziorrouh ◽  
Kathrin Sacher ◽  
Rajiv G. Tawar ◽  
Florian Emmerich ◽  
Christoph Neumann-Haefelin ◽  
...  
Keyword(s):  
T Cells ◽  
T Helper Cells ◽  
Cd4 T Cells ◽  
T Helper ◽  
Phenotypic Characteristics ◽  
Helper Cells ◽  
Chronic Hcv ◽  
Follicular T Helper Cells

Cyclophosphamide modulates CD4+ T cells into a T helper type 2 phenotype and reverses increased IFN-γ production of CD8+ T cells in secondary progressive multiple sclerosis

2004 ◽  
Vol 146 (1-2) ◽  
pp. 189-198 ◽  
Author(s):  
Arnon Karni ◽  
Konstantin Balashov ◽  
Wayne W. Hancock ◽  
Padmanabhan Bharanidharan ◽  
Michal Abraham ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Progressive Multiple Sclerosis ◽  
T Helper ◽  
Secondary Progressive ◽  
Ifn Γ ◽  
Helper Type

scholarly journals Pathological T Helper Polarization Requires Pre-existing Cross-Reactive Memory T Cells

2021 ◽  
Author(s):  
David Usharauli ◽  
Tirumalai Kamala
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Physiological Process ◽  
T Helper ◽  
Mhc Ii ◽  
Cytokine Milieu ◽  
Spiral Model ◽  
Memory Cd4 T Cells

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

scholarly journals The Diversity of Encephalitogenic CD4+ T Cells in Multiple Sclerosis and Its Animal Models

2019 ◽  
Vol 8 (1) ◽  
pp. 120 ◽  
Author(s):  
Benjamin Segal
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Association Studies ◽  
Critical Role ◽  
Genome Wide Association Studies ◽  
T Helper ◽  
Genome Wide ◽  
Disease Modifying Agents ◽  
Immunomodulatory Therapies

Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data from animal model experiments, genome-wide association studies, and immune profiles of individuals with MS. Furthermore, disease modifying agents that target lymphocytes significantly reduce the rate of MS clinical exacerbations. However, the properties of myelin-reactive CD4+ T cells that are critical for their pathogenic activities are not understood completely. This article reviews the literature on encephalitogenic CD4+ T cells, with an emphasis on T-helper (Th) lineage and cytokine production. An increased understanding of the spectrum of encephalitogenic T cells and how they differ from protective subsets is necessary for the development of the next generation of more effective and safer immunomodulatory therapies customized for individuals with MS and related disorders.

scholarly journals Distinct Expression of Inflammatory Features in T Helper 17 Cells from Multiple Sclerosis Patients

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 533 ◽  
Author(s):  
Alessia Capone ◽  
Manuela Bianco ◽  
Gabriella Ruocco ◽  
Marco De Bardi ◽  
Luca Battistini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Chronic Inflammatory Disease ◽  
T Helper ◽  
T Helper 17 ◽  
Inflammatory Status ◽  
Healthy Donors ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). T helper (Th) 17 lymphocytes play a role in the pathogenesis of MS. Indeed, Th17 cells are abundant in the cerebrospinal fluid and peripheral blood of MS patients and promote pathogenesis in the mouse model of MS. To gain insight into the function of Th17 cells in MS, we tested whether Th17 cells polarized from naïve CD4 T cells of healthy donors and MS patients display different features. To this end, we analysed several parameters that typify the Th17 profile during the differentiation process of naïve CD4 T cells obtained from relapsing-remitting (RR)-MS patients (n = 31) and healthy donors (HD) (n = 28). Analysis of an array of cytokines produced by Th17 cells revealed that expression of interleukin (IL)-21, tumour necrosis factor (TNF)-β, IL-2 and IL-1R1 is significantly increased in Th17 cells derived from MS patients compared to healthy donor-derived cells. Interestingly, IL-1R1 expression is also increased in Th17 cells circulating in the blood of MS patients compared to healthy donors. Since IL-2, IL-21, TNF-β, and IL-1R1 play a crucial role in the activation of immune cells, our data indicate that high expression of these molecules in Th17 cells from MS patients could be related to their high inflammatory status.

Methylome characterization of CD4+ T cells in multiple sclerosis — Establishing a role for miR-21 in autoimmune disease

2014 ◽  
Vol 275 (1-2) ◽  
pp. 112
Author(s):  
Sabrina Ruhrmann ◽  
Eliane Piket ◽  
Petra Bergman ◽  
Lara Kular ◽  
Julio Cesar Cetrulo Lorenzi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Autoimmune Disease ◽  
Cd4 T Cells

scholarly journals Immunological changes of T helper cells in flow cytometer‑sorted CD4+ T cells from patients with Hashimoto's thyroiditis

2018 ◽  
Author(s):  
Yanying Guo ◽  
Jazyra Zynat Zynat ◽  
Shuqing Xing ◽  
Liang Xin ◽  
Suli Li ◽  
...  
Keyword(s):  
T Cells ◽  
Hashimoto’S Thyroiditis ◽  
T Helper Cells ◽  
Cd4 T Cells ◽  
Flow Cytometer ◽  
Hashimoto's Thyroiditis ◽  
T Helper ◽  
Helper Cells ◽  
Immunological Changes
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