During the time I have been working on SIGNAL, I have implemented several experimental approaches to study the interaction between the nervous system and the immune system (i.e. the neuro-immune crosstalk). I have established fruitful collaborations with other labs which have been critical to developing these methods. The COVID19 pandemic had a significant impact on the progress of the action, and it hindered the originally planned progression of the experiments. However, with the support of the host lab (Andrew McKenzie’s research group) and institution (MRC Laboratory of Molecular Biology), I managed to continue my work and grow as a scientist.
We established eight different models to implement in our experiments exploring the neuro-immune crosstalk: three drug-based methods, two transgenic models, two chemogenetic models, and one optogenetic approach. We acquired, established, and bred several new mouse strains to be able to manipulate various subtypes of neurons and study their influence on immune cells. We also developed completely novel transgenic mouse strains that will help to target a subset of neurons in the intestine. These mouse strains have been valuable in the investigations for SIGNAL but they are also being used in other projects in the host lab.
By combining the aforementioned approaches with mouse models of type-2 immunity (i.e. the class of immune responses implicated in allergy and asthma) we were able to start elucidating how the neurons were regulating these immune reactions. We confirmed that sympathetic neurons are inhibiting inflammation in the lung, while other subtypes of neurons are promoting inflammation upon allergic reactions. In the latter, neuronal activation was enough to enhance the inflammatory potential of lymphocytes supporting their capacity to produce molecules that promote allergic inflammation.
The research proposed in this project encountered several experimental challenges that were aggravated by the ongoing COVID19 pandemic. While we continued undertaking and troubleshooting the approach proposed in the action, we also investigated the impact of neurons on the immune cells of another essential mucosal tissue: the female reproductive tract (FRT). The FRT is a mucosal site where the immune system must be tightly balanced to protect females from infection but allow pregnancy and tissue healing during the menstrual cycle. However, it is an understudied immune compartment. We discovered that the modulation exerted by subtypes of neurons on the lymphocytes in the FRT is opposite to the effect observed in the lung. Thus, indicating that the particulars of the local regulation of the neuro-immune crosstalk are not necessarily shared across different organs or tissues.
As part of my training and work, we published a review article to integrate and analyze our current knowledge on lymphocytes, asthma, and allergy, including the effect that the nervous system has on them. Moreover, I supervised and mentored several students in my host lab. I could provide my previous expertise in tumour immunology to contribute to the discovery of a new immune axis that promotes colorectal cancer progression.
