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Image: Cytokines (blue) secreted by T cells (red) stimulate monocytes (background) to feed
on Candida albicans hyphae (yellow).
Researchers from an international team of researchers have found that certain T cells can secrete cytokines, which are normally part of
the innate immune system.
As a result, they revealed some previously unknown properties of these immune cells that are associated
with autoimmune diseases as well as fighting fungal infections.
This study was published in Nature Immunology.
T cells are part of the adaptive immune system that recognizes foreign antigens and specifically fights pathogens
.
Different T cells perform different functions
in this process.
So-called T helper cells secrete cytokines that attract other immune cells to the site of infection and trigger inflammation
there.
However, T helper cells can also fight inflammation
.
A better understanding of these mechanisms can help develop treatments
against pathogens or autoimmune diseases.
Study leader Christina Zielinski explains: "We found a cytokine in Th17 cells, a subset of T helper cells, which was previously thought to be part of the
innate immune system.
" She is Head of the Department of Infectious Immunology at Leibniz-Hong Kong University and Professor
at Friedrich Schiller University Jena.
Cytokines, called IL-1α, are strong pro-inflammatory factors
.
"It's a signal molecule
for danger.
Even the smallest dose is enough to trigger a fever," Zielinski said
.
It is thought to be associated with
autoimmune diseases such as rheumatoid arthritis in children.
"We don't know how IL-1α is made in T cells and how it is released from the cell," said
first author Chao Ying-Yin.
The research was part of her doctoral dissertation, and she now works at an international biotech company in Munich, Germany, developing T-cell therapies
.
Through numerous experiments, the researchers eventually discovered that IL-1α, unlike other cytokines, is produced
by a multiprotein complex in T cells called inflammasomes.
This protein complex has very different roles
in other cells.
Zielinski said: "Until now, it was not known that human T cells had such an inflammatory body, and that it could be repurposed to produce IL-1α
.
"
Equally unexpected is the extracellular transport pathway
.
Alisa Puhach, the second author of the study, explains: "We found through knockout experiments that gasdermin E is the cause of
this.
" This molecule forms stomata
on the cell membrane.
The mechanism by which this inflammatory mediator is exported from T cells was previously unknown
.
The release of the cytokine IL-1α appears to be limited to a subset of Th17 cells; Other T helper cell types do not produce it
.
"Th17 cells play an important role in fungal infections," Zielinski said
.
Therefore, the team investigated whether IL-1α was also involved and was able to demonstrate that it was mainly Th17 cells that were antigenically specific
for infectious yeast.
Therefore, this subset of Th17 cells may be relevant
to defense against common yeast fungal infections.
In further research, the researchers now want to identify other diseases
in which pores-forming gas E plays a role in T cells.
In addition to other research groups at the Leibniz-Hong Kong University of Technology, researchers from the Technical University of Munich, the University of Freiburg, the Technical University of Graz in Austria and the University of Utrecht in the Netherlands also participated in the study
.
