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

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.

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

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.