Background: Precursor Th17 lineage cells expressing CD161 are implicated in rheumatoid arthritis pathogenesis. CD4+CD161+ T cells were found to accumulate in RA synovial fluid and tissue where they may acquire a non-classical T-helper 1 phenotype. The sole endogenous ligand for CD161 is lectin-like transcript 1 (LLT1). Previously, the LLT1-CD161 interaction was reported to co-stimulate T cell effector functions and to enhance IFN-γ production. This prompted us to investigate whether LLT1 is upregulated in the disease-affected joints. Objectives: We investigated the presence and identity of LLT1-expressing cells in RA synovial fluid and synovial tissue. Methods: Paired samples of peripheral blood and synovial fluid mononuclear cells (n=14) and digested synovial tissue cells (n=4) from late-stage rheumatoid arthritis patients were analyzed for LLT1 expression by flow cytometry. Paraffinembedded synovial tissue sections (n=6) were used for the immunohistochemical detection of LLT1. Results: In rheumatoid arthritis synovial fluid LLT1 expression was found upregulated in a subset of monocytes with a more differentiated, mature phenotype. In rheumatoid arthritis synovial tissue, LLT1-expressing cells were detected in the lining layer, sublining layer and in areas with lymphoid infiltrates. The LLT1 staining pattern resembled the pattern of CD68 staining. Flow cytometric analysis of digested synovial tissue confirmed LLT1 expression on CD68+ cells. Conclusions: This is the first study showing that surface-expressed LLT1 is present at the site of local inflammation in RA. The finding of LLT1 expression by macrophages in synovial tissue suggests potential crosstalk with CD161+ T-cells. Ligation of CD161-LLT1 on CD4 T cells and macrophages respectively, may contribute to modulation of their function at the level of the joint.
|Tijdschrift||Annals of the Rheumatic Diseases|
|Nummer van het tijdschrift||suppl.2|
|Status||Published - 1-jun-2015|