Distinct roles in NKT cell maturation and function for the different transcription factors in the classical NF‐κB pathway
| Autor: | Raffi Gugasyan, Raelene J. Grumont, Konstantinos Kyparissoudis, Dale I. Godfrey, Philip N. Tsichlis, Steve Gerondakis, Sanda Stankovic, Ashish Banerjee |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_treatment
Cellular differentiation Immunology Transcription Factor RelA Cell Count chemical and pharmacologic phenomena Thymus Gland Biology Cell Maturation Mice Proto-Oncogene Proteins medicine Animals Immunology and Allergy Transcription factor Cell growth NF-kappa B Cell Differentiation hemic and immune systems Cell Biology Natural killer T cell Proto-Oncogene Proteins c-rel Hedgehog signaling pathway Cell biology Mice Inbred C57BL Cytokine Cytokines Natural Killer T-Cells Signal Transduction |
| Zdroj: | Immunology & Cell Biology. 89:294-303 |
| ISSN: | 1440-1711 0818-9641 |
| DOI: | 10.1038/icb.2010.93 |
| Popis: | The nuclear factor (NF)-κB signalling pathway is known to be critical for natural killer T (NKT) cell differentiation; however, the role of individual NF-κB transcription factors and the precise developmental stages that they control remain unclear. We have investigated the influence of the classical NF-κB transcription factors NF-κB1, 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-κB signalling in early NKT cell development before NK1.1 expression, in contrast to earlier reports in which the classical NF-κB 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-κB1 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-κB1, 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-κB transcription factors, nor was this subset depleted, suggesting that NKT-17 cells are regulated independently of the NF-κB pathway. Thus, individual NF-κB 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. |
| Databáze: | OpenAIRE |
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