T helper (TH) cells are essential immune cells that help other immune cells function effectively. When activated in response to environmental stimuli, these cells can differentiate into either TH1 cells, which fight against viruses and intracellular pathogens, or TH2 cells, which fight against extracellular pathogens like bacteria and parasites.
However, scientists haven't fully understood whether infected tissue itself has any role in directing the optimal T cell differentiation in response to tissue infection.
Research has shown that virally infected neurons play a significant role by promoting the development of TH1 cells and inhibiting TH2 cells during viral infections. This communication between infected neurons and the immune system happens through molecules called neuropeptides, which interact with specific receptors on T cells to guide their fate. This process is crucial for the body to effectively control viral infections.
The findings, published in the journal Nature, show that neuroimmune communication plays a crucial role in determining T cell fate, establishing a novel link between infected tissue (neurons) and the differentiation of T cell subsets.
The research team investigated the regulatory mechanisms that guide the optimal differentiation of T cells into specific lineages while inhibiting others. To do this, they used a technique called single-cell RNA sequencing (scRNA-seq) to study how genes are expressed over time, looking at two types of immune cells (TH1-TH2) in a cell culture system. They also applied CRISPR screening to identify which regulators help control T cell fate development into Th1 vs. Th2 cells.
By combining various gene and cellular biology techniques, they demonstrated that the neuropeptide receptor RAMP3 plays a key role in how T cells develop using preclinical models.
The team showed that neuroimmune circuits, influenced by neuropeptides and their receptors, play a pivotal role in determining T cell fate. They also explored how neuropeptides ensure optimal T cell differentiation and drive robust antiviral responses.
The study suggests that changes to neuroimmune circuits may help balance different types of T cell and lead to better immune responses. For example, previous research has shown an imbalance of TH2 differentiation over TH1 is correlated with increased death in patients with COVID-19.
Targeting the neuroimmune pathways that regulate T cell fate decisions may offer new therapeutic opportunities for patients with severe COVID-19 infections, cancer and other autoimmune diseases.