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Role of ILC2 in infection: cross-section of the small intestine after infection with Strongyloides
brasilensis.
The goblet cells in the intestine produce more mucus (yellow) to repel worms
.
Mucus production is triggered by a type 2 immune response, involving not only ILC2 (unstained) but also clustered cells (magenta).
The latter is located in the intestinal villi, finger-like projections of the intestinal mucosa protruding into the intestinal lumen (the nucleus of the mucosa is turquoise in color).
Inflammation and increased mucus secretion are typical symptoms of
helminth infection and allergies.
This immune response involves our innate immune cells, but their exact function is not fully understood
.
The human immune system is made up of two interrelated branches: the adaptive immune system, which learns something new from each infection and evolves throughout life, and the innate immune system, which is less specialized but responds particularly quickly and effectively
.
The cells of the innate immune system are located on the mucous membranes of the respiratory tract and intestines, and they form the first line
of defense where pathogens enter.
These cells include group 2 innate lymphoid cells (ILC2s for short), which are active in the intestines of patients with parasitic diseases and in
the respiratory tract of allergy patients.
"Innate lymphoid cells were discovered about a decade ago, and we already know a lot about them, but their exact function in immune system mechanisms is not yet fully understood," explains
Dr.
Christoph Klose.
He is the head of the independent primary research group of Amy Noether at the Charité Institute of Microbiology, Infectious Diseases and Immunology, which focuses on the regulation of type 2 immune responses
through neuropeptides and neurotransmitters.
"There is a group of adaptive immune cells — T cells — that perform some similar functions as part of the type 2 immune response, so it was previously thought that ILC2s might be redundant and easily replaced
by T cells.
"
However, recently published research disproves this theory
.
Using animal models and state-of-the-art molecular methods such as single-cell sequencing, scientists can zoom in on individual cells and analyze their molecular states, and they have elucidated the core function
of ILC2s2.
Dr.
Klose explains: "When ILC2s are lost, a specific type of immune cell called eosinophils cannot develop
properly.
This relationship was unknown before, which was a big surprise
.
Eosinophils are involved in the inflammatory process
in tissues.
The scientists also found that ILC2s2 has an important effect
on the ability of epithelial cells to promote mucus production and excrete the parasite.
In our tests that examine the immune response to nematode infection, the absence of ILC2s is clearly visible
.
There is only limited mucus production in the tissues, and the parasite can no longer fight effectively"
.
In further experiments, the researchers examined the symptoms of allergic asthma and found that these symptoms improved
when ILC2s were missing.
Dr Klose said: "This could be the starting point
for future research aimed at developing potential allergy therapies.
Through our research, we were able to show that 2 groups of innate lymphoid cells are essential cogs in the immune system mechanism and cannot be replaced
without affecting the immune response.
In future research projects, Dr.
Klose and his team hope to investigate whether innate lymphoid cells regulate other aspects of
the immune response.
Non-redundant functions of group 2 innate lymphoid cells