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.

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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
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article

The NF ‐ κB transcription factor RelA directs mucosal‐associated invariant T‐cell development

Darryl N. Johnson, Hanno Nel, Sebastian Scheer, Ranjeny Thomas et al.
Immunology and Cell Biology
Immune Cell Function and Interaction
article

The NF ‐ κB transcription factor RelA directs mucosal‐associated invariant T‐cell development

Darryl N. Johnson, Hanno Nel, Sebastian Scheer, Ranjeny Thomas, David P. Fairlie, Vanessa L. Bryant, 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
article en

Abstract

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.

Immunology and Cell Biology
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)
Openalex Percentile: Top 43%
Immune Cell Function and Interaction
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