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

Paulina Chalan,Bart-Jan Kroesen,Annemieke M H Boots,Johan Bijzet,Elisabeth Brouwer,Minke G Huitema,Luis Graca

doi:10.1371/journal.pone.0132436

Paulina Chalan, Bart-Jan Kroesen + Show 5 more

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https://doi.org/10.1371/journal.pone.0132436

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Abstract

ObjectivesPrecursor Th17 lineage cells expressing CD161 are implicated in Rheumatoid Arthritis (RA) pathogenesis. CD4+CD161+ T-cells accumulate in RA joints and may acquire a non classical Th1 phenotype. The endogenous ligand for CD161 is lectin-like transcript 1 (LLT1). CD161/LLT1 ligation may co-stimulate T-cell IFN-γ production. We investigated the presence and identity of LLT1-expressing cells in RA synovial fluid (SF) and synovial tissue (ST). We also assessed levels of soluble LLT1 (sLLT1) in different phases of RA development.MethodsPaired samples of peripheral blood mononuclear cells (MC) and SFMC (n = 14), digested ST cells (n = 4) and ST paraffin sections (n = 6) from late-stage RA were analyzed for LLT1 expression by flow cytometry and immunohistochemistry. sLLT1 was measured using a sandwich ELISA. Sera and SF from late-stage RA (n = 26), recently diagnosed RA patients (n = 39), seropositive arthralgia patients (SAP, n = 31), spondyloarthropathy patients (SpA, n = 26) and healthy controls (HC, n = 31) were assayed.ResultsIn RA SF, LLT1 was expressed by a small proportion of monocytes. In RA ST, LLT1-expressing cells were detected in the lining, sublining layer and in areas with infiltrates. The LLT1 staining pattern overlapped with the CD68 staining pattern. FACS analysis of digested ST confirmed LLT1 expression by CD68+ cells. Elevated systemic sLLT1 was found in all patient groups.ConclusionsIn RA joints, LLT1 is expressed by cells of the monocyte/macrophage lineage. Serum levels of sLLT1 were increased in all patient groups (patients with early- and late-stage RA, seropositive arthralgia and spondyloarthropathy) when compared to healthy subjects.

Highlights

Human T lymphocytes expressing killer cell lectin-like receptor CD161 (NKR-P1A) have gained increased appreciation over the last decade
In rheumatoid arthritis (RA) joints, lectin-like transcript 1 (LLT1) is expressed by cells of the monocyte/macrophage lineage
Serum levels of soluble LLT1 (sLLT1) were increased in all patient groups when compared to healthy subjects

Summary

Introduction

Human T lymphocytes expressing killer cell lectin-like receptor CD161 (NKR-P1A) have gained increased appreciation over the last decade. CD161+ Th17-lineage cells were implicated in the pathogenesis of Crohn's disease [1], giant cell arteritis [2] and psoriasis [3] by accumulation and active IL-17 expression in the disease-affected sites. CD161 + cells can acquire a non classical Th1 phenotype, manifested by IFN-γ and T-bet expression, thought to be driven by IL-12 at the site of inflammation [4,5]. The sole endogenous ligand for CD161 is lectin-like transcript 1 (LLT1) [7,8]. Despite the growing evidence supporting a role of CD161+ T-cells in autoimmune pathology, no studies have yet addressed the expression of lectin-like transcript 1 in autoimmune conditions

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