Impaired lymph node stromal cell function during the earliest phases of rheumatoid arthritis.

Autor: Hähnlein JS; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands.; Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands., Nadafi R; Department of Molecular Cell Biology and Immunology, VU Medical Centre, Amsterdam, the Netherlands., de Jong T; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands.; Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands., Ramwadhdoebe TH; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands.; Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands., Semmelink JF; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands.; Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands., Maijer KI; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands., Zijlstra IA; Department of Radiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands., Maas M; Department of Radiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands., Gerlag DM; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands.; Present address: Clinical Unit Cambridge, GlaxoSmithKline, Cambridge, UK., Geijtenbeek TBH; Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands., Tak PP; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands.; Present address: Ghent University, Ghent, Belgium.; Present address: University of Cambridge, Cambridge, UK.; Present address: GlaxoSmithKline, Stevenage, UK., Mebius RE; Department of Molecular Cell Biology and Immunology, VU Medical Centre, Amsterdam, the Netherlands., van Baarsen LGM; Amsterdam Rheumatology & immunology Centre (ARC), Department of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands. e.g.vanbaarsen@amc.uva.nl.; Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, the Netherlands. e.g.vanbaarsen@amc.uva.nl.
Jazyk: angličtina
Zdroj: Arthritis research & therapy [Arthritis Res Ther] 2018 Feb 26; Vol. 20 (1), pp. 35. Date of Electronic Publication: 2018 Feb 26.
DOI: 10.1186/s13075-018-1529-8
Abstrakt: Background: Systemic autoimmunity can be present years before clinical onset of rheumatoid arthritis (RA). Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) regulate immune responses through their intimate connection with leucocytes. We postulate that malfunctioning of LNSCs creates a microenvironment in which normal immune responses are not properly controlled, possibly leading to autoimmune disease. In this study we established an experimental model for studying the functional capacities of human LNSCs during RA development.
Methods: Twenty-four patients with RA, 23 individuals positive for autoantibodies but without clinical disease (RA risk group) and 14 seronegative healthy control subjects underwent ultrasound-guided inguinal lymph node (LN) biopsy. Human LNSCs were isolated and expanded in vitro for functional analyses. In analogous co-cultures consisting of LNSCs and peripheral blood mononuclear cells, αCD3/αCD28-induced T-cell proliferation was measured using carboxyfluorescein diacetate succinimidyl ester dilution.
Results: Fibroblast-like cells expanded from the LN biopsy comprised of fibroblastic reticular cells (gp38 + CD31 - ) and double-negative (gp38 - CD31 - ) cells. Cultured LNSCs stably expressed characteristic adhesion molecules and cytokines. Basal expression of C-X-C motif chemokine ligand 12 (CXCL12) was lower in LNSCs from RA risk individuals than in those from healthy control subjects. Key LN chemokines C-C motif chemokine ligand (CCL19), CCL21 and CXCL13 were induced in LNSCs upon stimulation with tumour necrosis factor-α and lymphotoxin α 1 β 2 , but to a lesser extent in LNSCs from patients with RA. The effect of human LNSCs on T-cell proliferation was ratio-dependent and altered in RA LNSCs.
Conclusions: Overall, we developed an experimental model to facilitate research on the role of LNSCs during the earliest phases of RA. Using this innovative model, we show, for the first time to our knowledge, that the LN stromal environment is changed during the earliest phases of RA, probably contributing to deregulated immune responses early in disease pathogenesis.
Databáze: MEDLINE
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