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Chronically stimulated human MAIT cells are unexpectedly potent IL‐13 producers

Year: 2019
Type: article
Abstract: Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize antigens derived from riboflavin biosynthesis. In addition to anti-microbial functions, human MAIT cells are associated with cancers, autoimmunity, allergies and inflammatory disorders, although their role is poorly understood. Activated MAIT cells are well known for their rapid release of Th1 and Th17 cytokines, but we have discovered that chronic stimulation can also lead to potent interleukin (IL)-13 expression. We used RNA-seq and qRT-PCR to demonstrate high expression of the IL-13 gene in chronically stimulated MAIT cells, and directly identify IL-13 using intracellular flow cytometry and multiplex bead analysis of MAIT cell cultures. This unexpected finding has important implications for IL-13-dependent diseases, such as colorectal cancer (CRC), that occur in mucosal areas where MAIT cells are abundant. We identify MAIT cells near CRC tumors and show that these areas and precancerous polyps express high levels of the IL-13 receptor, which promotes tumor progression and metastasis. Our data suggest that MAIT cells have a more complicated role in CRC than currently realized and that they represent a promising new target for immunotherapies where IL-13 can be a critical factor.
DOI: 10.1111/imcb.12281
Authors: Jason Kelly, Yosuke Minoda, Tobias Meredith, Garth Cameron, Marie‐Sophie Philipp, Daniel G Pellicci, Alexandra J Corbett, Christian Kurts, Daniel HD Gray, Dale I Godfrey, George Kannourakis, Stuart P Berzins
Institutions: Federation University, The University of Melbourne, Peter Doherty Institute, Murdoch Children's Research Institute, University of Bonn, Walter and Eliza Hall Institute of Medical Research, Australian Research Council
Language: English
Subfield: Immunology
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: Australian Government, Cass Foundation, Deutsche Forschungsgemeinschaft, Lung Foundation Australia, Federation University Australia, Medical Research Council, Australian Research Council, National Health and Medical Research Council
Awards: Targeting Cell Death Pathways in Immune Pathology and Cancer, ARC Centre of Excellence in Advanced Molecular Imaging, The Mechanisms of Epithelial Cell Survival that Govern Thymus Function, Unconventional T cells in health and disease, G4209227257, G5006260125, Development and selection of MAIT cells, How the immune system recognises vitamin B-based allergies, Antigen presentation, recognition and the immune response, Targeting Caspase 8 in T-Cell Homeostasis and Disease
OpenAlex ID: W2964200043
FWCI: 3.877
Cites: 43
Cited by: 72
Related to: 10