8 May 2014

Immune cells use steroids to self-regulate

Type 2 T-helper cells produce a steroid to turn themselves off

Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system. These cells appear to produce a steroid to turn themselves off once the infection has been cleared.

Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system. These cells appear to produce a steroid to turn themselves off once the infection has been cleared. [National Institute of Allergy and Infectious Diseases (NIAID)]

Researchers at the Wellcome Trust Sanger Institute and the European Bioinformatics Institute (EMBL-EBI) have discovered that some immune cells turn themselves off by producing a steroid. The findings have implications for the study of cancers, autoimmune diseases and parasitic infections.

The scientists in the Sanger Institute-EBI Single-Cell Genomics Centre looked at the activity of genes in Th2 immune cells during parasitic infection and saw that, at a certain point, these cells produce a steroid called pregnenolone, which is involved in suppressing the immune response.

"We were really surprised to see that these immune cells are producing a steroid. In cell culture, we see that the steroids play a part in regulating T cell proliferation," says Dr Bidesh Mahata, a member of Sarah Teichmann's research group at the Sanger Institute and EMBL-EBI. "We had already seen that T-helper cells were producing steroids, but initially we were blind - what was going on?"

" We confirmed our findings that pregnenolone inhibits both Th cell proliferation and B cell immunoglobulin class switching. We think this points to the idea that Th2 cells differentiate into steroid-producing cells as part of a larger mechanism to bring the immune system back into balance. "

Dr Bidesh Mahata

The study used single-cell sequencing data and sophisticated statistical methods to confirm for the first time that the immune cells are able to self-regulate once they have finished battling infection.

"Because we had access to data from single-cell sequencing experiments, we could conduct deep statistical analyses on a very large and comprehensive dataset," explains Dr Sarah Teichmann, Faculty member of the Sanger Institute and Senior Group Leader at EMBL-EBI. "That pointed us to the genes involved in pregnenolone production at the point when Th2 cells are being produced, and we could deduce that the Th2 cells themselves were involved in immunosuppression."

The researchers suggest that bringing the immune system back into balance is an intrinsic part of this particular immune response.

"We confirmed our findings experimentally, showing that pregnenolone inhibits both Th cell proliferation and B cell immunoglobulin class switching," adds Dr Mahata. "We think this points to the idea that Th2 cells differentiate into steroid-producing cells as part of a larger mechanism to bring the immune system back into balance."

The findings from this study are strengthened by those of the Gelfand group at National Jewish Health in Denver, US. The next step for the team is to investigate how the process starts, what other tissues are involved and which types of infection give rise to this response.

Notes to Editors

Publication details

  • Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.

    Mahata B, Zhang X, Kolodziejczyk AA, Proserpio V, Haim-Vilmovsky L, Taylor AE, Hebenstreit D, Dingler FA, Moignard V, Göttgens B, Arlt W, McKenzie AN and Teichmann SA

    Cell reports 2014;7;4;1130-42

Funding

Please see the paper for a full list of funding bodies.

Participating Centres

Please see the paper for a full list of participating centres.

The European Bioinformatics Institute

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