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Updated: Jan 17, 2026
Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase G6PI-Induced RA Mice
Published on: January 31, 2020
Targeting CD161 inhibitory receptors enhances NK cell-mediated changes in synovial fibroblast function in rheumatoid
Junqin Lu1, Jiale Song2, Hongwei Yu1
1Department of Orthopedics, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222000, China.
Objective:
Rheumatoid arthritis (RA) is a chronic autoimmune disease that still lacks reliable biomarkers. The mechanistic role of CD161 as an inhibitory receptor in RA pathogenesis and its potential for predicting therapeutic responses require further investigation.
Methods:
We combined RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and clinical sample analyses to characterize the specific expression of CD161 in RA. We constructed a collagen-induced arthritis (CIA) model and injected NK cells into the joint cavity. Additionally, we stimulated fibroblast-like synoviocytes (FLS) with IFN-γ in vitro, followed by whole-genome sequencing and in vitro cell co-culture assays, to explore the mechanism by which CD161 regulates FLS function.
Results:
CD161 was specifically overexpressed in synovial NK cells from RA patients and negatively correlated with NK cell-derived IFN-γ. Using a CD56+ NK cell line with regulated CD161 expression, we demonstrated that intra-articular injection of these cells alleviated CIA synovitis severity to a certain extent. In vitro, IFN-γ stimulation of FLS followed by whole-genome sequencing, combined with CD56+ NK cell-FLS co-culture experiments, revealed that CD161 inhibited the tumor-like properties of FLS, likely via mechanisms involving IFN-γ and the PI3K-AKT pathway.
Conclusion:
CD161 is a potential biomarker for RA. Targeted inhibition of CD161 in NK cells alleviates synovial inflammation in RA, highlighting its therapeutic potential.
Insights
CD161, a receptor on NK cells, shows promise as a biomarker for rheumatoid arthritis (RA). Targeting CD161 in NK cells can reduce joint inflammation, offering new therapeutic strategies for RA.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited reliable biomarkers.
- The role of CD161 as an inhibitory receptor in RA pathogenesis and its predictive potential for treatment responses needs further clarification.
Purpose of the Study:
- To investigate the expression of CD161 in RA.
- To explore the mechanistic role of CD161 in RA pathogenesis.
- To assess the therapeutic potential of targeting CD161 in RA.
Main Methods:
- Combined RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and clinical sample analyses.
- Utilized a collagen-induced arthritis (CIA) model with NK cell injections.
- Performed in vitro stimulation of fibroblast-like synoviocytes (FLS) with IFN-γ, whole-genome sequencing, and co-culture assays.
Main Results:
- CD161 was overexpressed in synovial NK cells from RA patients, correlating negatively with NK cell-derived IFN-γ.
- Intra-articular injection of NK cells with regulated CD161 expression partially alleviated CIA synovitis.
- CD161 was found to inhibit FLS tumor-like properties via IFN-γ and the PI3K-AKT pathway.
Conclusions:
- CD161 emerges as a potential biomarker for rheumatoid arthritis.
- Targeting CD161 in NK cells demonstrates therapeutic potential by alleviating synovial inflammation in RA.
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