Written by Jan Grabowski, TWINCORE – Zentrum für Experimentelle und Klinische Infektionsforschung
TLR8 is expressed on monocytes and cDCs, but not pDCs, from patients with systemic sclerosis (SSc). Source: Arthritis & Rheumatology (2024). DOI: 10.1002/art.42964
Systemic sclerosis is an autoimmune disease that causes inflammation primarily in the skin, lungs, heart, and other internal organs. The disease is considered rare, and little is still known about its onset and progression.
A team led by Junior Research Group Leader Theresa Grahlmann from the Center for Experimental and Clinical Infection Research (TWINCORE) in collaboration with the departments of Rheumatology, Immunology and Dermatology at the Hannover Medical School investigated the role of specific immune cell populations in patients with systemic sclerosis.
The researchers found that certain signaling pathways are also active in different cells than previously thought, and they report their findings in the journal Arthritis & Rheumatology.
Patients with systemic sclerosis suffer from skin changes that are caused by the patient’s own immune system, not by a virus or bacteria. This is why the disease is called an autoimmune disease. Systemic sclerosis is classified as a rare disease because it affects a very small number of people. Therefore, the progression of the disease is not yet fully understood.
Studies of patients’ immune cells have recently revealed that the gene for the protein Toll-like receptor 8 (TLR8) is more strongly activated in certain cells than in healthy individuals. TLR8 is a cellular receptor that is typically activated by certain viruses and triggers an immune cell response.
The Hannover team wanted to further explore this finding at the level of actual protein amounts. To do this, they first isolated plasmacytoid dendritic cells from the skin and blood of 10 patients with systemic sclerosis.
“We studied these cells using flow cytometry,” says Christine Ehlers, a doctoral student in TWINCORE’s Translational Immunology research group, “which allows us to measure the concentrations of receptors and immune messengers, so-called cytokines, inside the cells.”
Kristin Ehlers (left) and Theresa Grahlmann in the lab. Photo by TWINCORE/Grabowski
The researchers compared their measurements with those of healthy subjects and with those of patients with Sjögren’s syndrome, another autoimmune disease, and detected no differences in TLR8 levels.
The scientists then stimulated the receptor by adding different agonists, which sets off a signaling chain that leads to the production of cytokines in the cell and further stages of the immune response, but this series of experiments did not change the levels of TLR8 or the amount of cytokines produced.
“Although we know that TLR8 is functional in principle, we were able to show that this receptor plays no role in plasmacytoid dendritic cells in systemic sclerosis,” says research group leader Grahlmann.
“Yet, we did find one difference,” Ehlers added. “Monocytes from scleroderma samples showed increased production of IL-10 after TLR8 activation. This phenomenon was not observed in the Sjögren’s syndrome control group.”
IL-10 stands for interleukin 10. This cytokine has anti-inflammatory effects, but it also has pro-fibrotic effects, meaning it promotes the abnormal growth of connective tissue. “IL-10 may contribute to the skin fibrosis that is a hallmark of systemic sclerosis,” says Grahlman.
Graalman’s team of researchers has made great strides in understanding what causes systemic sclerosis, “but unfortunately, the numbers of patients are so small that we cannot yet draw any direct conclusions about treatment,” Graalman said.
“However, a better molecular understanding of the inflammatory response during these diseases is the first step toward new and better treatments for affected patients.”
Further information: Christine Ehlers et al. “Toll-like receptor 8 is expressed on monocytes in contrast to plasmacytoid dendritic cells and mediates aberrant interleukin-10 responses in patients with systemic sclerosis, arthritis, and rheumatism (2024)” DOI: 10.1002/art.42964
Provided by: TWINCORE – Zentrum für Experimentelle und Klinische Infektionsforschung
Citation: Systemic sclerosis study finds protein TLR8 influences production of disease-related cytokines (September 23, 2024) Retrieved September 23, 2024 from https://medicalxpress.com/news/2024-09-sclerosis-protein-tlr8-production-disease.html
This document is subject to copyright. It may not be reproduced without written permission, except for fair dealing for the purposes of personal study or research. The content is provided for informational purposes only.
