Glycoprotein Ib-CD11b + monocyte-derived macrophages mediate atherosclerosis-exacerbated psoriatic inflammation.

BACKGROUND

Psoriasis is a systemic inflammatory skin disease affecting 2-3 % of the global population, with significant cardiovascular comorbidities. A complex inflammatory interaction exists between psoriasis and atherosclerosis, but the exact mechanism remains unclear.

METHODS

To elucidate this relationship, we collected skin biopsies from treatment-naïve patients with comorbid psoriasis and atherosclerosis underwent single-cell RNA sequencing, integrated with public atherosclerosis datasets. Bioinformatics analysis identified cell populations and interactions. Validation included immunohistochemistry, immunofluorescence, in vitro functional assays with isolated patient macrophages and platelets, and an in vivo imiquimod-induced psoriasis mouse model treated with a CD11b agonist.

RESULTS

Single-cell RNA sequencing identified significantly increased CD11b + monocyte-derived macrophages in psoriasis lesions comorbid with atherosclerosis, exhibiting proinflammatory M1 polarization and enriched IL-17/chemokine signaling. These macrophages shared transcriptional signatures with monocytes in atherosclerotic plaques. In vivo, CD11b agonism (ADH-503) exacerbated imiquimod-induced psoriatic inflammation. Mechanistically, platelet-derived GPIb promoted macrophage M1 polarization via the GPIb-CD11b axis, evidenced by GPIb upregulation correlating with psoriasis severity (PASI), spatial co-localization in perivascular regions, and dose-dependent M1 marker induction by recombinant GPIb. GPIbhi monocytes from atherosclerotic patients showed enhanced proinflammatory pathways, revealing a shared mechanism driving inflammation in both diseases.

CONCLUSIONS

Collectively, CD11b + monocyte-derived macrophages are central to the interplay between atherosclerosis and psoriasis through the GPIb-CD11b axis. Targeting GPIb with specific drugs to control atherosclerosis may enhance the efficacy of inflammatory control in psoriasis.