CARDIOVASCULAR AND CERECYTOKINE PRODUCING B CELLS SKEW MACROPHAGES TOWARDS A PRO-INFLAMMATORY PHENOTYPE IN GIANT CELL ARTERITIS
Authors: J. C. Graver et al.
Macrophages and T cells are well recognized players in the pathogenesis of GCA while B cells are often not taken into account. This Dutch group analyzed the cytokine profile of circulating and lesional B cells.
Cryopreserved peripheral blood mononuclear cells of 11 untreated GCA patients and of 15 matched healthy controls (HC) were cultured and assessed for IL6, TNFα, IFNγ, LTβ and regulatory B cell-related cytokines (IL10) production using flow cytometry. Skewing of macrophages by B cell products was analyzed using THP-1 cells, a monocytic cell line. To assess local cytokine production, temporal artery (TA; n=11) and aorta tissue samples (n=10) of histologically-proven GCA patients were stained to detect CD20, IL6, TNFα, IFNγ, LTβ, and IL10 expression. B cells from untreated GCA patients showed an enhanced percentage of IL6+ B cells and of IL6+TNFα+ B cells compared to stimulated B cells from HC. In addition, soluble factors, secreted by GCA stimulated B cells, skewed macrophages towards a pro-inflammatory phenotype with enhanced expression of cytokines. Furthermore, these macrophages also showed higher expression of the tissue remodelling factor MMP9 and the pro-angiogenic factor YKL40. At the site of vascular inflammation, B cells were detected in the regions with cytokine expression in both the TA and aorta of GCA patients.
The study demonstrates a potential contributory, proinflammatory role of B cells in GCA. In part this is based on production of IL-6. Remarkably, IL-6 was originally named «B-cell stimulatory factor 2» (BSF-2) as of its effect on B (lineage) cells. Taken together the data suggest an autocrine effect of IL-6 on B cells, and they add a rational for IL-6 targeting therapies.