The irresistible CCL17

September 13, 2018

The chemotactic protein CCL17 attracts immune cells to where they are currently needed. Doctors have long known: A high level of this substance in the body indicates an allergic reaction. A team of scientists led by the University of Bonn has now discovered a completely new function: CCL17 also influences signal transmission in the brain. There may even be a molecular link to autism. The results have now been published in the journal "Glia".

Chemotactic cytokines, chemokines for short, are signaling proteins that act like an attractant and ensure, for example, that immune cells migrate from the bloodstream into the tissues. The chemokine CCL17 is known to increase inflammation and is associated with allergic diseases. A high level of CCL17 in the blood is regarded by doctors as a diagnostic marker of ongoing allergic reactions such as atopic eczema. The further the research on chemokines progresses, however, the more functions are discovered. Thus, an earlier joint study by the Universities of Münster and Bonn showed that animals with a defect in the expression of the receptor for CCL17 have behavioral problems: For example, they were unable to build proper nests like their normally developed mates.

"These behavioral changes indicated that CCL17 not only affects the immune system but perhaps also the brain," explains the corresponding author of the study, Prof. Dr. Irmgard Förster from the LIMES Institute at the University of Bonn, who is also a member of the Cluster of Excellence "ImmunoSensation". If there is such a connection, which cells in the brain produce CCL17? This question was investigated by doctoral student Lorenz Fülle and Irmgard Förster, together with scientists from the Institute of Cellular Neurosciences around Prof. Dr. Christian Henneberger, Dr. Annett Halle from the German Center for Neurodegenerative Diseases (DZNE) and Dr. Judith Alferink from the University of Münster.

Through a genetic modification, the researchers coupled the release of CCL17 with the production of a fluorescent dye that illuminated all cells that produce the chemokine. The scientists additionally stimulated CCL17 production by simulating an infection using a substance contained in bacterial cell membranes. The production sites of the chemokine in the brain were then clearly visible under the microscope. "CCL17 is mainly produced by neurons of the hippocampus," reports lead author Lorenz Fülle. This structure, which is shaped like a seahorse, is present on the right and left side of the brain, and fulfills an important function in tasks such as orientation and memory formation.

Scientists blocked the gene for CCL17

As a next step, the scientists blocked the gene for CCL17 production and observed the effect. In the absence of the chemokine, the microglial cells in these "knockout" mice were significantly smaller and there were only half as many as in untreated control animals. Microglial cells have long been known as immune cells of the brain, where they take responsibility as "health guards" for the disposal of cell debris and infectious agents. Meanwhile, it has been shown that these "scavenger cells" also directly support the work of the neurons independently of their phagocytic activity.

In order to investigate the effect of CCL17 on the function of neurons, scientists in the laboratory of Prof. Dr. Christian Henneberger at the Institute of Cellular Neurosciences (University of Bonn Medical School) examined neuronal signaling in the brain. Henneberger: "The experiments indicate that CCL17 attenuates signal transmission in the hippocampal region of the brain." Since autism in humans is also associated with elevated levels of CCL17 in the blood, CCL17 could also play a role in this developmental disorder, for example due to an infection or an allergic reaction in early childhood. "But so far these are speculations," says Förster. "The exact effects of CCL17 have yet to be demonstrated by further research."
Publication: Lorenz Fülle, Nina Offermann, Jan Niklas Hansen, Björn Breithausen, Anna Belen Erazo, Oliver Schanz, Luca Radau, Fabian Gondorf, Konrad Knöpper, Judith Alferink, Zeinab Abdullah, Harald Neumann, Heike Weighardt, Christian Henneberger, Annett Halle and Irmgard Förster: CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons, GLIA, DOI: 10.1002/glia.23507

Media contact:

Prof. Dr. Irmgard Förster
Cluster of Excellence ImmunoSensation
University of Bonn
Tel. +49 (0)228/7362780 or 7362789

University of Bonn

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to