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Compartment-Specific NK Cell Phenotypes Reveal Distinct Maturation and Activation States in Inflammatory Arthritis
Franca Sophie Deicher1,2, Tarik Exner3, Maren Claus4
1Department of Rheumatology, University Hospital Düsseldorf, Medical Faculty of Heinrich-Heine-University, Dusseldorf, Germany.
Journal of Innate Immunity
|December 9, 2025
Summary
This study reveals distinct changes in natural killer (NK) cells within the joints and blood of arthritis patients, highlighting their interactions with neutrophils in inflamed tissues.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Synovial natural killer (NK) cells are implicated in arthritis pathogenesis.
- NK cells influence inflammation through cytokine secretion and synovial fibroblast activation.
Purpose of the Study:
- To characterize systemic and local inflammatory profiles of NK cell subsets in arthritis.
- To investigate physical cell-cell interactions of NK cells within inflamed joints.
Main Methods:
- Paired analysis of peripheral blood (PB) and synovial fluid (SF) using spectral flow cytometry.
- Application of cellular interaction mapping to study cell-cell interactions in situ.
Main Results:
- SF-NK cells showed local enrichment of immature and activated subsets with tissue-resident markers.
- PB-NK cells exhibited systemic alterations, with fewer immature and more pro-inflammatory mature subsets.
- Cellular interaction mapping identified significant NK/neutrophil interactions in patients' joints, with B-cells, T-cells, and monocytes showing negligible interactions.
Conclusions:
- Arthritis involves both systemic and local NK cell subset alterations, influenced by developmental stages and immune regulation.
- Neutrophils are identified as a primary interaction partner for NK cells in the inflamed joint environment.
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