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

Szabolcs Elias, Angelika Schmidt, David Gomez-Cabrero, Jesper Tegner

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish (US)
Pages (from-to)1-24
Number of pages24
JournalJournal of Immunology Research
Volume2021
DOIs
StatePublished - Jul 3 2021

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint

Dive into the research topics of 'Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells'. Together they form a unique fingerprint.

Cite this