Keeping the Balance: How the immune system is shaped by environmental microbes and the allergic signals sensed

The interplay of our bodies and the environment profoundly shapes our health, in particular by the recognition and response to diverse microorganisms. These interactions have a direct impact on the development of our immune system. The lack of exposure to a diverse array of microorganisms, such as those present in our microbiota, has been associated with dysregulation of our immune barriers, promoting detrimental inflammatory conditions like autoimmunity and allergies. Previous intervention studies have shown that modulation of the skin microbiota using forest-derived soil in humans correlated with a higher immune regulatory cytokine pattern in peripheral blood. However, the cellular mechanisms controlling this immune modulation are not completely understood. We evaluated the immune response to autoclaved and non-autoclaved forest-derived soil in the mouse immune system by cytokine profiling, cellular phenotyping, gene expression characterization, and in vitro stimulation of immune cells. Our results demonstrate that environmental soil exposure induces an immune response in mice characterized by anti- inflammatory traits and lower inflammatory signatures upon re-stimulation.

Furthermore, in the skin we find Langerhans cells which serve as a communication link between the outside world and our innate and adaptive immune system. Langerhans cells can directly recognize pathogens and sense cytokines released by the epithelial barrier to direct the adaptive immune response. The induction of the pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is linked to an unbalanced immune response, such as the one seen in atopic dermatitis. The understanding of how this signal is sensed by Langerhans cells is crucial to improving diagnostics and developing new therapeutical strategies. Using specific TSLP-induced inflammation in mice, we evaluated TSLP receptor dynamics during early inflammation. We demonstrated that Langerhans cells express both receptor chains for TSLP signaling, and that under TSLP induction, one of these receptors’ chains, the TSLPR, undergo a positive expression loop.

In conclusion, our studies shed light on the immunological effect of environmental soil exposure and its potential as a therapeutic approach to prevent and control inflammatory diseases. Furthermore, the improved understanding of TSLP signaling in vivo has the potential to generate diagnostic tools and prevent the pro-inflammatory mechanisms behind diseases such as atopic dermatitis.