REGγ controls Th17 cell differentiation and autoimmune inflammation by regulating dendritic cells.
Cell Mol Immunol
; 17(11): 1136-1147, 2020 11.
Article
de En
| MEDLINE
| ID: mdl-31511643
ABSTRACT
Interleukin-17A (IL-17A)-producing helper T (Th17) cells are a subset of CD4+ T cells that play important pathological roles in autoimmune diseases. Although the intrinsic pathways of Th17 cell differentiation have been well described, how instructive signals derived from the innate immune system trigger the Th17 response and inflammation remains poorly understood. Here, we report that mice deficient in REGγ, a proteasome activator belonging to the 11S family, exhibit significantly deteriorated autoimmune neuroinflammation in an experimental autoimmune encephalomyelitis (EAE) model with augmented Th17 cell polarization in vivo. The results of the adoptive transfer of CD4+ T cells or dendritic cells (DCs) suggest that this phenotype is driven by DCs rather than T cells. Furthermore, REGγ deficiency promotes the expression of integrin αvß8 on DCs, which activates the maturation of TGF-ß1 to enhance Th17 cell development. Mechanistically, this process is mediated by the REGγ-proteasome-dependent degradation of IRF8, a transcription factor for αvß8. Collectively, our findings delineate a previously unknown mechanism by which REGγ-mediated protein degradation in DCs controls the differentiation of Th17 cells and the onset of an experimental autoimmune disease.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Autoantigènes
/
Cellules dendritiques
/
Auto-immunité
/
Différenciation cellulaire
/
Proteasome endopeptidase complex
/
Cellules Th17
/
Inflammation
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Cell Mol Immunol
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2020
Type de document:
Article