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Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis
OBJECTIVES: Precursor 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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492745/ https://www.ncbi.nlm.nih.gov/pubmed/26147876 http://dx.doi.org/10.1371/journal.pone.0132436 |
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author | Chalan, Paulina Bijzet, Johan Huitema, Minke G. Kroesen, Bart-Jan Brouwer, Elisabeth Boots, Annemieke M. H. |
author_facet | Chalan, Paulina Bijzet, Johan Huitema, Minke G. Kroesen, Bart-Jan Brouwer, Elisabeth Boots, Annemieke M. H. |
author_sort | Chalan, Paulina |
collection | PubMed |
description | OBJECTIVES: Precursor 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. METHODS: Paired 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. RESULTS: In 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. CONCLUSIONS: In 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. |
format | Online Article Text |
id | pubmed-4492745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44927452015-07-15 Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis Chalan, Paulina Bijzet, Johan Huitema, Minke G. Kroesen, Bart-Jan Brouwer, Elisabeth Boots, Annemieke M. H. PLoS One Research Article OBJECTIVES: Precursor 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. METHODS: Paired 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. RESULTS: In 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. CONCLUSIONS: In 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. Public Library of Science 2015-07-06 /pmc/articles/PMC4492745/ /pubmed/26147876 http://dx.doi.org/10.1371/journal.pone.0132436 Text en © 2015 Chalan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chalan, Paulina Bijzet, Johan Huitema, Minke G. Kroesen, Bart-Jan Brouwer, Elisabeth Boots, Annemieke M. H. Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis |
title | Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis |
title_full | Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis |
title_fullStr | Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis |
title_full_unstemmed | Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis |
title_short | Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis |
title_sort | expression of lectin-like transcript 1, the ligand for cd161, in rheumatoid arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492745/ https://www.ncbi.nlm.nih.gov/pubmed/26147876 http://dx.doi.org/10.1371/journal.pone.0132436 |
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