Hobit turns immune cells into killers

Date:
August 30, 2021
Source:
University of Wu"rzburg
Summary:
Against infections, tumors and inflammations, immune cells are
locally positioned as rapid reaction forces in the organs of the
body. On site, they specialize and take on various tasks.



FULL STORY ==========================================================================
When pathogens invade the human body, a rapid response is required. At the forefront of the immune response are special immune cells. They reside
in various tissues such as the lungs, liver, skin and intestines, where
they take up the fight against invaders at an early stage. Their name:
innate lymphoid cells, or ILCs for short.


==========================================================================
A special property of these cells: They do not have to be alerted first in lymphoid organs, like many other immune cells, in order to then migrate
to their place of action. Instead, they settle in the tissues and organs shortly after birth and remain there permanently.

Single cell mRNA atlas of ILC1 ILCs can arise in tissues from immature precursor cells and mature into operational immune cells. This was
recently shown by scientists of the Max Planck Research Group at the
Institute of Systems Immunology of Julius- Maximilians-Universita"t
(JMU) Wu"rzburg in Bavaria, Germany. Until now, it was unclear how this maturation proceeds in detail.

"We wanted to understand how immature ILCs become effector cells that
can, for example, kill tumour cells or fight infections with the help
of cytokines," explains Professor Georg Gasteiger, chair and head of
the Max Planck Research Group at the JMU Institute of Systems Immunology.

To do this, the Wu"rzburg researchers studied the group of ILC1s that
play a role in viral infections and in tumour defence. They have recorded
all mRNA molecules of individual ILC1s in the liver and created a virtual
cell atlas from these analyses.



========================================================================== Division of tasks: supply, helper and killer cells Based on these
"molecular fingerprints," the researchers recognised that there are
specialised cells within the ILC1 that share their tasks: "We found
cells that can multiply very quickly and thus provide for replenishment
of ILCs. In the process, they specialise into so-called helper or killer
ILCs." Gasteiger's team found that the helper cells produce a wide range
of messenger substances (cytokines) that play a role in the early phase
of infections, for example. The killer cells, on the other hand, are
armed with molecules that allow them to recognise and kill tumour cells.

"Until now, it was thought that these cells were different types of ILCs" explains Christin Friedrich. The postdoctoral researcher from Gasteiger's
team is the first author of the publication, which appeared in the journal Nature Immunology. "But our data show that they are different degrees of specialisation that can arise in each organ from the same supply troops."
Can killer ILCs be made therapeutically useful? "Interestingly, however,
ILCs only develop into killer cells in some tissues, although our data
show that they have the potential to do so in all tissues" explains
Gasteiger.

"We have initial evidence that this development is actively suppressed
in some tissues, possibly to avoid tissue damage or inflammation. We
now want to understand how we can therapeutically activate the killer
cells, for example to improve immune control of developing tumours
and metastases. We also want to investigate which molecules the
ILCs can use to recognise tumours and how they behave in different
tissues during infections." Transcription factor Hobit drives
specialisation Christin Friedrich adds: "Our work shows how the
transcription factor Hobit drives specialisation to mature effector
cells. It is exciting that Hobit is also expressed in other killer
cells of the human immune system. Based on our results, the function
of Hobit in these defence cells can now be explored, how they mature
and how they might be induced to fight tumours in different tissues." ========================================================================== Story Source: Materials provided by University_of_Wu"rzburg. Original
written by Robert Emmerich. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Christin Friedrich, Renske L. R. E. Taggenbrock, Re'mi
Doucet-Ladeve`ze,
Gosia Golda, Rebekka Moenius, Panagiota Arampatzi, Natasja
A. M. Kragten, Katharina Kreymborg, Mercedes Gomez de Agu"ero,
Wolfgang Kastenmu"ller, Antoine-Emmanuel Saliba, Dominic
Gru"n, Klaas P. J. M. van Gisbergen, Georg Gasteiger. Effector
differentiation downstream of lineage commitment in ILC1s is
driven by Hobit across tissues. Nature Immunology, 2021; DOI:
10.1038/s41590-021-01013-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210830123230.htm

--- up 16 weeks, 3 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)