Publications & Reports

Distinct roles in NKT cell maturation and function for the different transcription factors in the classical NF-kappaB pathway.

Stankovic S, Gugasyan R, Kyparissoudis K, Grumont R, Banerjee A, Tsichlis P, Gerondakis S, Godfrey DI
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.


The nuclear factor (NF)-kappaB signalling pathway is known to be critical for natural killer T (NKT) cell differentiation; however, the role of individual NF-kappaB transcription factors and the precise developmental stages that they control remain unclear. We have investigated the influence of the classical NF-kappaB transcription factors NF-kappaB1, c-Rel and RelA on NKT cell development and function, using gene-deleted mice. Individually, none of these factors were essential for the requirement of NF-kappaB signalling in early NKT cell development before NK1.1 expression, in contrast to earlier reports in which the classical NF-kappaB pathway was globally disrupted. Instead, we found that each factor played a non-redundant role in later stages of NKT cell maturation and function. Although NF-kappaB1 deficiency resulted in a moderate reduction in mature NK1.1+ NKT cells, this was found to be more subtle than previously reported. RelA deficiency had a more profound effect on the NK1.1+ stage of NKT cell development, whereas c-Rel-deficient mice had normal NKT cell numbers. All three factors (NF-kappaB1, RelA and c-Rel) were necessary for normal NKT cell cytokine production. Notably, IL-17, which is produced by a specific subset of NKT cells (NKT-17 cells), defined as NK1.1(-)CD4(-), was not impaired by a lack of these individual NF-kappaB transcription factors, nor was this subset depleted, suggesting that NKT-17 cells are regulated independently of the NF-kappaB pathway. Thus, individual NF-kappaB family members have a largely redundant role in early NKT cell development, but each of them has an important and distinct role in NKT cell maturation and/or function.


  • Journal: Immunology and Cell Biology
  • Published: 01/02/2011
  • Volume: 89
  • Issue: 2
  • Pagination: 294-303