The <scp>NF</scp> ‐ <scp>κB</scp> transcription factor <scp>RelA</scp> directs mucosal‐associated invariant T‐cell development
Mucosal-associated invariant T (MAIT) cells are characterized by rapid responses to nonpeptide antigens via invariant T-cell receptors (TCR), and expression of an "effector-like" T-cell phenotype. The transcription factor promyelocytic leukemia zinc finger (PLZF) is crucial for defining the function of MAIT cells and other unconventional T cells; however, the transcriptional programs that direct MAIT cell development are not fully elucidated. Here, we show that the canonical NF-κB transcription factor RelA is critical for MAIT cell thymic development, but not responsiveness to antigen, whereas NF-κB1 and c-Rel make more limited contributions. MAIT cell development is also impaired in the absence of the linear ubiquitin signaling complex (LUBAC), an upstream regulator of NF-κB signaling, implicating this pathway in establishing the MAIT cell pool. Collectively, these data suggest LUBAC and NF-κB signals as elements of the transcriptional network controlling MAIT cell development.
Authors
- Darryl N. Johnson (ORCID: https://orcid.org/0000-0003-3205-0371)
- Hanno Nel
- Sebastian Scheer (ORCID: https://orcid.org/0000-0002-9716-5009)
- Ranjeny Thomas
- David P. Fairlie (ORCID: https://orcid.org/0000-0002-7856-8566)
- Vanessa L. Bryant (ORCID: https://orcid.org/0000-0002-4697-7410)
- Zaph Colby
- DH Gray
- Raelene J. Grumont
- S Gerondakis
- Charis E. Teh
- Hui-Fern Koay
- Jeffrey Yw Mak
- Thomas S Fulford
- Lorraine A O'Reilly
- Dale I Godfrey
Institutions
- Translational Research Institute (AU)
- The Royal Melbourne Hospital (AU)
- The University of Queensland (AU)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Discovery Institute (US)
- Australian Regenerative Medicine Institute (AU)
- Peter Doherty Institute (AU)
- Monash University (AU)
Publication Details
- Journal
- Immunology and Cell Biology
- Published
- 2026-02-23
- DOI
- https://doi.org/10.1111/imcb.70096
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.00