T Cell–Intrinsic Function of the Noncanonical NF-κB Pathway in the Regulation of GM-CSF Expression and Experimental Autoimmune Encephalomyelitis Pathogenesis
| Autor: | Xiaofei Zhou, Mako Nakaya, Jiayi Yu, Wei Jin, Xuhong Cheng, Shao Cong Sun |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Naive T cell
Effector medicine.medical_treatment T cell Immunology Experimental autoimmune encephalomyelitis NF-κB Biology medicine.disease Molecular biology Cell biology chemistry.chemical_compound Transactivation Cytokine medicine.anatomical_structure chemistry Humoral immunity medicine Immunology and Allergy |
| Zdroj: | The Journal of Immunology. 193:422-430 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1303237 |
| Popis: | The noncanonical NF-κB pathway induces processing of the NF-κB2 precursor protein p100, and thereby mediates activation of p52-containing NF-κB complexes. This pathway is crucial for B cell maturation and humoral immunity, but its role in regulating T cell function is less clear. Using mutant mice that express a nonprocessible p100, NF-κB2lym1, we show that the noncanonical NF-κB pathway has a T cell–intrinsic role in regulating the pathogenesis of a T cell–mediated autoimmunity, experimental autoimmune encephalomyelitis (EAE). Although the lym1 mutation does not interfere with naive T cell activation, it renders the Th17 cells defective in the production of inflammatory effector molecules, particularly the cytokine GM-CSF. We provide evidence that p52 binds to the promoter of the GM-CSF–encoding gene (Csf2) and cooperates with c-Rel in the transactivation of this target gene. Introduction of exogenous p52 or GM-CSF to the NF-κB2lym1 mutant T cells partially restores their ability to induce EAE. These results suggest that the noncanonical NF-κB pathway mediates induction of EAE by regulating the effector function of inflammatory T cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|