CR6-interacting factor 1 controls autoimmune arthritis by regulation of signal transducer and activator of transcription 3 pathway and T helper type 17 cells.
Immunology
; 156(4): 413-421, 2019 04.
Article
in En
| MEDLINE
| ID: mdl-30585643
ABSTRACT
CR6-interacting factor 1 (CRIF1) is a nuclear protein that interacts with other nuclear factors and androgen receptors, and is implicated in the regulation of cell cycle progression and cell growth. In this study, we examined whether CRIF1 exerts an immunoregulatory effect by modulating the differentiation and function of pathogenic T cells. To this end, the role of CRIF1 in rheumatoid arthritis, a systemic autoimmune disease characterized by hyperplasia of synovial tissue and progressive destruction of articular cartilage structure by pathogenic immune cells [such as T helper type 17 (Th17) cells], was investigated. p3XFLAG-CMV-10-CRIF1 was administered to mice with collagen-induced arthritis 8 days after collagen type II immunization and the disease severity and histologic evaluation, and osteoclastogenesis were assessed. CRIF1 over-expression in mice with collagen-induced arthritis attenuated the clinical and histological signs of inflammatory arthritis. Furthermore, over-expression of CRIF1 in mice with arthritis significantly reduced the number of signal transducer and activator of transcription 3-mediated Th17 cells in the spleen as well as osteoclast differentiation from bone marrow cells. To investigate the impact of loss of CRIF1 in T cells, we generated a conditional CRIF1 gene ablation model using CD4-cre transgenic mice and examined the frequency of Th17 cells and regulatory T cells. Deficiency of CRIF1 in CD4+ cells promoted the production of interleukin-17 and reduced the frequency of regulatory T cells. These results suggest a role for CRIF1 in modulating the activities of Th17 cells and osteoclasts in rheumatoid arthritis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arthritis, Experimental
/
Signal Transduction
/
Cell Cycle Proteins
/
STAT3 Transcription Factor
/
Th17 Cells
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Immunology
Year:
2019
Document type:
Article
Affiliation country:
South Korea