The NF-kappaB transcription factor RelA directs mucosal-associated invariant T-cell development

Fulford, TS; Koay, HF; Grumont, R; Johnson, DN; Scheer, S; Nel, HJ; Thomas, R; Mak, JY; Fairlie, DP; Teh, CE; Gray, DH; Bryant, VL; Zaph, C; O&#39;Reilly, LA; Gerondakis, S; Godfrey, DI

Author(s): Fulford, TS; Koay, HF; Grumont, R; Johnson, DN; Scheer, S; Nel, HJ; Thomas, R; Mak, JY; Fairlie, DP; Teh, CE; Gray, DH; Bryant, VL; Zaph, C; O'Reilly, LA; Gerondakis, S; Godfrey, DI;
Details: Publication Year 2026-04,Volume 104,Issue #4,Page 329-344
Journal Title: Immunology and Cell Biology
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-kappaB transcription factor RelA is critical for MAIT cell thymic development, but not responsiveness to antigen, whereas NF-kappaB1 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-kappaB signaling, implicating this pathway in establishing the MAIT cell pool. Collectively, these data suggest LUBAC and NF-kappaB signals as elements of the transcriptional network controlling MAIT cell development.
Publisher: Wiley
Keywords: *Mucosal-Associated Invariant T Cells/immunology/cytology/metabolism; Animals; *Transcription Factor RelA/metabolism/genetics; Signal Transduction; *Cell Differentiation/immunology; Mice; Mice, Inbred C57BL; NF-kappa B/metabolism; Promyelocytic Leukemia Zinc Finger Protein/metabolism; Receptors, Antigen, T-Cell/metabolism; Thymus Gland/immunology/cytology; Mice, Knockout; Lubac; MAIT cells; NF-kappaB; RelA; development
Research Division(s): Immunology; Infection and Global Health
PubMed ID: 41732015
Publisher's Version: https://doi.org/10.1111/imcb.70096
Open Access at Publisher's Site: https://doi.org/10.1111/imcb.70096
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-03-16 01:38:29

Last Modified: 2026-04-27 03:54:31