NKG2D ligands in inflammatory joint diseases: analysis in human samples and mouse models

Abstract

Background NKG2D ligands (NKG2DLs) are stress-inducible molecules involved in multiple inflammatory settings. In this work, we quantified MICA, an NKG2DL, in the synovial fluid of patients suffering various arthritides and measured Nkg2dLs gene expression in murine models of acute joint inflammation. Methods Soluble MICA (sMICA) was quantified by ELISA is synovial fluids harvested from patients suffering osteoarthritis, rheumatoid arthritis, psoriatic arthritis, calcium pyrophosphate crystal arthritis, urate crystal arthritis and reactive arthritis. Transcripts encoding murine NKG2DLs were quantified by RT-qPCR in the joints of mouse models of rheumatoid arthritis, urate crystal arthritis and osteoarthritis. Results Marked overproduction of sMICA was observed in the synovial fluid of RA patients. Mouse studies highlighted the complex transcriptional regulation of Nkg2d ligands encoding genes depending on the inflammatory setting and microenvironment Conclusions sMICA quantification could be an interesting biomarker to identify acute inflammation in RA patients in which classical markers (ie, anti-citrullinated protein antibodies, ACPA) are undetectable.

Senescence in osteoarthritis: from mechanism to potential treatment

“…RA synovial cells abnormally expressed the stress-inducible MIC ligands of NKG2D, which stimulated CD4 + CD28 -T cell cytokine production and proliferation [153]. However, the expression of Rae1 (a ligand of NKG2D in mice) is induced in all inflammatory joint diseases except collagenase-induced OA (CIOA) mouse models [154], which indicates that the NKG2D-NKG2D ligand interaction is absent in CIOA. It is unclear whether this interaction exists in other types of OA (Fig.…”