How do antimicrobial peptides alter T cell cytokine production?

Antimicrobial peptides are released by neutrophils, mast cells and epithelial cells during infectious and inflammatory disease. They have many effects on innate and adaptive immune cells. We have recently shown that one antimicrobial peptide in particular, cathelicidin, drives differentiation of the Th17 subset of T cells (Minns Nature Communications 2021). We have also shown that this peptide-induced T cell differentiation causes autoimmune disease in a model of Multiple Sclerosis (Smith PLOS Biology 2022). This is exciting because it has shown that these ubiquitous peptides may have far greater impact on adaptive immunity than we had previously imagined.

Now, we want to investigate this process in much greater depth. We know that cathelicidin gets into T cells and alters cytokine expression – particularly IL-17F and IFN-γ. We do not know how this occurs or which signalling pathways are involved. In this project we will use a variety of techniques to decipher how peptide exposure alters the pathways leading to production of these cytokines. We will work out what this means for a number of models of disease – including autoimmune, infection and cancer models.

The student will use techniques including multi-colour and spectral flow cytometry, confocal microscopy, ELISA, isolation and culture of T cells and analysis of RNA sequencing data. Animal handling and in vivo models of disease will be involved in the project. They will be fully trained in all these techniques as well as in statistics, coding, presentation skills, writing skills, and data management.