Feb 28, 2018

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

Arthritis Research & Therapy
Janine S HähnleinLisa G M van Baarsen

Abstract

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. 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. 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 characteris...Continue Reading

Mentioned in this Paper

5-(6)-carboxyfluorescein diacetate succinimidyl ester
Immune Response
Pathogenic Aspects
Autoantibodies
Small Inducible Cytokine A21
Stromal Cell-Derived Factor 1
Research
Mononuclear Cells
Pathogenesis
Tumor Necrosis Factor-alpha

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