Expression of Lectin-like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis

Paulina Chalan¹, Johan Bijzet², Minke G. Huitema³, Bart-Jan Kroesen⁴, Elisabeth Brouwer¹ and Annemieke M.H. Boots¹, ¹Dept. of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, ²Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, Netherlands, ³Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, ⁴Dept. of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Basic research and rheumatoid arthritis (RA)

Session Information

Title: Innate Immunity and Rheumatic Disease: Signaling Mechanisms

Session Type: Abstract Submissions (ACR)

Background/Purpose

Precursor Th17 lineage cells expressing CD161 are implicated in rheumatoid arthritis (RA) pathogenesis. CD4+CD161+ T cells were found to accumulate in RA synovial fluid (SF) and tissue (ST) where they may acquire a non-classical T-helper 1 phenotype. The 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 arthritic joints. To that end we investigated the presence and identity of LLT1-expressing cells in RA synovial fluid and synovial tissue.

Methods

Paired samples of peripheral blood (PB) and SF mononuclear cells (n=14) and digested ST cells (n=4) from late-stage rheumatoid arthritis patients were analyzed for LLT1 expression by flow cytometry. Cell suspensions were stained with fluorochrome labeled anti-human LLT1, CCR2, CD14, HLA-DR, CD1a, CD16, CD163, CD1c, CD141, CD62L, CD86, CD303. Cells were analyzed using an LSR II flow cytometer and data analysis was performed with Kaluza® analysis software. Paraffin-embedded ST sections (n=6) were used for the immunohistochemical detection of LLT1. To further characterize LLT1 expressing cells, consecutive tissue sections were stained with the antibodies recognizing macrophage marker CD68, T cell marker CD3 and B cell marker CD20

Results

In rheumatoid arthritis SF LLT1 expression was found upregulated in a subset of monocytes with a more differentiated, mature phenotype. In RA ST, LLT1-expressing cells were detected in the lining layer, sublining layer and in areas with lymphoid infiltrates. The LLT1 staining pattern overlapped with the CD68 (macrophages) staining pattern. Flow cytometric analysis of digested ST confirmed that LLT1 is expressed on CD68+ cells.

Conclusion

This is the first study showing that surface-expressed LLT1 is present in arthritic joints 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.

Disclosure:

P. Chalan,
None;

J. Bijzet,
None;

M. G. Huitema,
None;

B. J. Kroesen,
None;

E. Brouwer,
None;

A. M. H. Boots,
None.

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-lectin-like-transcript-1-the-ligand-for-cd161-in-rheumatoid-arthritis/