Bronchial asthma is one of the most common chronic childhood diseases. While the prevalence is high in urban areas with high hygiene standards, children who grow up on farms or in rural areas are often protected from allergies and asthma.
In particular, early contact with a number of microbial components, such as the cell wall component lipopolysaccharide (LPS), seems to provide this protective effect. In order to prevent excessive inflammatory reactions, for example via the NF-κB signaling pathway, the immune system can adapt to these stimuli, which are usually harmless to the human body, through tolerance mechanisms.
With the help of four pediatric cohorts consisting of two cross-sectional studies from Europe and China and two prospective birth cohorts, blood samples from 250 asthmatic and healthy children from a total of 2,168 study participants were compared. The anti-inflammatory, negative regulator of the NF-κB signaling pathway TNFAIP3 (tumor necrosis factor-alpha-induced protein 3, also known as A20) was identified as a potential biomarker for the development of asthma.
The TNFAIP3 expression was already significantly reduced at birth in umbilical cord blood of healthy newborns who developed asthma up to the age of 10 years. TNFAIP3 was also found to be reduced in blood in children with manifest asthma between the ages of 4 and 15. By stimulating the blood samples with "asthma-protective" farm extracts, an anti-inflammatory effect of these extracts could be demonstrated. The expression of anti-inflammatory factors was upregulated, while the expression of anti-inflammatory genes was reduced by stimulation. The reduced expression of the protective regulator TNFAIP3 in asthmatic children was even raised to the basic level of healthy children by stimulation of farm extracts.
According to the researchers, this study contributes to a better understanding of asthma development through misregulation of anti-inflammatory and pro-inflammatory components of the innate immune system. On the other hand, it helps to decipher the mechanisms of environmentally mediated protection. These results could play an important role in future prevention strategies and prediction of asthma development via the expression of TNFAIP3. Due to the anti-inflammatory effects in manifest asthmatics, there is even a realistic possibility for a future therapeutic application of farm extracts.
Krusche J, et al.Schaub B. (2019), TNFAIP3 is a key player in childhood asthma development and environment-mediated protection. Journal of Allergy and Clinical Immunology, in press.