Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 97, Issue 8, Pages 689-699Publisher
WILEY
DOI: 10.1111/imcb.12281
Keywords
Colorectal cancer; human immunity; IL-13; MAIT cells; tumor immunity
Categories
Funding
- National Health and Medical Research Council of Australia (NHMRC) [1113293, 1140126, 1145888, 1121325]
- Australian Research Council (ARC) [CE140100011]
- CASS Foundation [8510]
- FECRI
- Lung Foundation Australia
- Australian Government Research Training Program (RTP) Fee-Offset Scholarship through Federation University Australia
- Deutsche Forschungsgemeinschaft [GRK2168]
- Bonn and Melbourne Research and Graduate School (BoMeRanG) Program
- CSL Centenary Fellowship
- ARC Future Fellowship [FT160100083]
- Australian NHMRC Senior Research Fellowship [1158024]
- NHMRC Senior Principal Research Fellowship [1117766]
- Dorevitch Cancer Research Fellowship
- National Health and Medical Research Council of Australia [1140126, 1158024, 1145888, 1121325] Funding Source: NHMRC
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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.
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