Extended Data Fig. 8: CCL3 and FOXP3 mRNA expression in human plaques and synopsis of the proposed pathway.
(a) mRNA expression of CCL3 in advanced atherosclerotic plaques (n = 16) or early (n = 13) lesions derived from GSE28829 dataset; (b) mRNA expression of CCL3 in human atheroma plaque (atheroma) or paired distant macroscopically intact tissue (adjacent) derived from GSE43292 dataset (n = 32 each); (c) CCL3 mRNA expression in symptomatic (n = 8) or asymptomatic (n = 6) patients with carotid and coronary plaques derived from GSE11138 dataset; (d,e) Quantification of CCL3 (d) and FOXP3 (e) mRNA copy numbers normalized to housekeeping mRNA (105 GAPDH or β-actin mRNA copies, respectively) in atherosclerotic lesions of carotid atherectomy specimens from symptomatic (d, e n = 13) or asymptomatic (d, n = 16; e, n = 15) patients using real-time PCR; (a-e) Data represent mean ± SEM. Two-sided P values as indicated versus corresponding controls, as analyzed by unpaired Student’s t-test (a-c), or Mann Whitney U test (d, e); (f) Pathway synopsis (I.) Sterile inflammation triggers the activation of a subset of cDCs, which respond by releasing CCL17. (II.) In turn, CCL17 binds to CCR8 on cDCs (autocrine) and on CD4+ T cells (paracrine) to stimulate an upregulation of CCL3 expression and release. (III.) Subsequently, CCL3 interacts with CCR1 on naïve T cells, thereby blocking the differentiation and expansion of Tregs.
