Peripheral blood monocytes (PBMCs) of healthy volunteers exposed to oligomeric S100A4 (oS100A4) showed increased IL-1β, IL-6, and TNFα in response to the liposaccharide of Escherichia coli (LPS E.coli). RNASEq upon β-glucan or oS100A4 revealed similar changes in chemokines/cytokines and epigenetic effectors; 17 epigenetic effectors correlated with chemokine/cytokine gene expression; PRDM8 was associated with more chemokine and cytokine transcripts. Knockdown of PRDM8 abolished trained immunity induced by oS100A4. In RA, plasma S100A4 correlated with increased CSF2, and increased PRDM8 transcription in PBMCs was associated with increased plasma CCL5 and IL-6, as well as therapy resistance.
In addition, citrullinated vimentin and the lipopolysaccharide of Porphyromonas gingivalis (LPS P.gingivalis) induced training in most healthy controls, as suggested by the significantly increased levels of secreted interleukin-6 (IL-6), the chemokine CXCL-1, and the Macrophage Inflammatory Protein 3a. The native vimentin had significantly less training capacities compared to the citrullinated one. In RA, while the levels of released IL-6 were similar to controls after stimulation with LPS E.coli, we observed a significantly increased immune response after stimulation with LPS P. gingivalis, citrullinated vimentin or oS100A4.