Identifying novel MAIT cell expansion strategies to mitigate graft-versus-host disease

Aspects of this project would be suitable for Honours, Masters, MPhil, MD and PhD students. Email the supervisor to discuss suitability.

Background

 Mucosal-associated invariant T cells (MAIT cells) are an important regulatory subset which possess potent anti-microbial functions, primarily due to their rapid, diverse and expansive cytokine production. Initially, MAIT cells were shown to respond to vitamin B-derived microbial metabolites presented by the MHC class I-like molecule MR1, however increasing evidence now shows activation via MR1-independent mechanisms such as cytokine-mediated pathways. We have shown recipient MAIT cells control gut barrier function, in part via interleukin-17A, to attenuate pathogenic T cell responses in the colon and protect against the development of acute graft-versus-host disease.

Aim

This project aims to validate newly identified candidates that expand MAIT cells in vivo.

Methods

This project will involve ex vivo murine and human PBMC functional assays, high-parameter flow cytometry, cellular metabolism assays, gut organoid cultures and immunofluorescence microscopy.

Project Potential

This translationally-focused research builds on strong preclinical findings and is pertinent for the development of MAIT cell-based immunotherapeutic approaches to treat gut GVHD in the clinic.