Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets

2016 ◽  
Vol 23 (7) ◽  
pp. 1025-1030 ◽  
Author(s):  
Catharina C Gross ◽  
Andreas Schulte-Mecklenbeck ◽  
Uta Hanning ◽  
Anita Posevitz-Fejfár ◽  
Catharina Korsukewitz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Lymphoid Cell ◽  
Flow Cytometric Analysis ◽  
Cell Subset ◽  
Distinct Pattern ◽  
T Helper ◽  
Innate Lymphoid Cell ◽  
Disease Manifestation ◽  
Gm Csf ◽  
Lesion Topography

Background: Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). Objective: To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Methods: Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Results: Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing TH1 cells or interleukin (IL)-17-producing TH17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of TH17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Conclusions: Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis

2004 ◽  
Vol 10 (5) ◽  
pp. 494-498 ◽  
Author(s):  
Juan Feng ◽  
Tatsuro Misu ◽  
Kazuo Fujihara ◽  
Saburo Sakoda ◽  
Yuji Nakatsuji ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Flow Cytometric Analysis ◽  
Cell Subset ◽  
Phosphodiesterase Inhibitor ◽  
Interleukin 4 ◽  
Clinical Effects ◽  
Autoimmune Encephalomyelitis ◽  
Flow Cytometric ◽  
Mrna Ratio ◽  
Killer T Cells

We investigated the immunoregulatory effects of ibudilast, a nonselective phosphodiesterase inhibitor, at a clinically applicable dose (60 mg/day p.o. for four weeks) in multiple sclerosis (MS) patients. Sensitive real-time PCR for quantifying cytokine mRNA in the blood CD4- cells revealed that the ibudilast monotherapy significantly reduced tumour necrosis factor-a and interferon (IFN)-g mRNA and the IFN-g/interleukin-4 mRNA ratio, suggesting a shift in the cytokine profile from Th1 toward Th2 dominancy. In a flow cytometric analysis, natural killer T cells, which have been reported to relate to Th2 responses in MS and its animal model (experimental autoimmune encephalomyelitis), increased significantly after the therapy. None of the significant immunological changes were seen in healthy subjects or untreated MS patients. Ibudilast may be a promising therapy for MS and its clinical effects warrant further study.

Targeting cellular fatty acid synthesis limits T helper and innate lymphoid cell function during intestinal inflammation and infection

2020 ◽  
Vol 14 (1) ◽  
pp. 164-176 ◽  
Author(s):  
Panagiota Mamareli ◽  
Friederike Kruse ◽  
Chia-wen Lu ◽  
Melanie Guderian ◽  
Stefan Floess ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Lymphoid Cell ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Acid Synthesis ◽  
Cellular Fatty Acid ◽  
T Helper ◽  
Innate Lymphoid Cell

A distinct GM-CSF+ T helper cell subset requires T-bet to adopt a TH1 phenotype and promote neuroinflammation

2020 ◽  
Vol 5 (52) ◽  
pp. eaba9953
Author(s):  
Javad Rasouli ◽  
Giacomo Casella ◽  
Satoshi Yoshimura ◽  
Weifeng Zhang ◽  
Dan Xiao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Cell ◽  
Cell Mass ◽  
Cell Subset ◽  
Interferon Γ ◽  
T Helper ◽  
Gm Csf ◽  
Macrophage Colony

Elevation of granulocyte-macrophage colony-stimulating factor (GM-CSF)–producing T helper (TH) cells has been associated with several autoimmune diseases, suggesting a potential role in the pathogenesis of autoimmunity. However, the identity of GM-CSF–producing TH cells has not been closely examined. Using single-cell RNA sequencing and high-dimensional single-cell mass cytometry, we identified eight populations of antigen-experienced CD45RA−CD4+ T cells in blood of healthy individuals including a population of GM-CSF–producing cells, known as THGM, that lacked expression of signature transcription factors and cytokines of established TH lineages. Using GM-CSF-reporter/fate reporter mice, we show that THGM cells are present in the periphery and central nervous system in a mouse model of experimental autoimmune encephalomyelitis. In addition to GM-CSF, human and mouse THGM cells also expressed IL-2, tumor necrosis factor (TNF), IL-3, and CCL20. THGM cells maintained their phenotype through several cycles of activation but up-regulated expression of T-bet and interferon-γ (IFN-γ) upon exposure to IL-12 in vitro and in the central nervous system of mice with autoimmune neuroinflammation. Although T-bet was not required for the development of THGM cells, it was essential for their encephalitogenicity. These findings demonstrate that THGM cells constitute a distinct population of TH cells with lineage characteristics that are poised to adopt a TH1 phenotype and promote neuroinflammation.

scholarly journals The Transcription Factor AHR Prevents the Differentiation of a Stage 3 Innate Lymphoid Cell Subset to Natural Killer Cells

Cell Reports ◽  
2014 ◽  
Vol 8 (1) ◽  
pp. 150-162 ◽  
Author(s):  
Tiffany Hughes ◽  
Edward L. Briercheck ◽  
Aharon G. Freud ◽  
Rossana Trotta ◽  
Susan McClory ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Lymphoid Cell ◽  
Cell Subset ◽  
Innate Lymphoid Cell ◽  
Killer Cells

scholarly journals GM-CSF and CXCR4 define a T helper cell signature in multiple sclerosis

2019 ◽  
Vol 25 (8) ◽  
pp. 1290-1300 ◽  
Author(s):  
Edoardo Galli ◽  
Felix J. Hartmann ◽  
Bettina Schreiner ◽  
Florian Ingelfinger ◽  
Eirini Arvaniti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Gm Csf

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.

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.

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