Metabolic Syndrome in Psoriasis Is Associated With Upregulation of CXCL16 on Monocytes and a Dysbalance in Innate Lymphoid Cells

Abstract

Psoriasis is frequently associated with the metabolic syndrome and occurs more often in obese individuals. In order to understand innate immune mechanisms mediating this inflammatory pattern we investigated expression of the chemokine and lipid scavenger receptor CXCL16 in patients with psoriasis and associated comorbidities. CXCL16 expression was enhanced on all monocyte subsets in psoriatic patients compared with healthy controls and positively correlated with psoriasis activity and severity index, body mass index and the risk for cardiovascular disease indicated by PROCAM score. The intensity of CXCL16 expression on monocytes further correlated with their capability to phagocytose oxidized LDL indicating the possibility to transform into foam cells in atherosclerotic plaques. Patients with psoriasis and atherosclerosis or obesity displayed elevated numbers of innate lymphoid cells in blood with specific increase of the IFN-γ or IL-17 producing ILC1 and ILC3 subpopulations. The expression of the CXCL16 receptor, CXCR6, was increased in ILCs and co-expressed with CCR6 but not CCR7 indicating their migratory potential to psoriatic skin or adipose tissue that is characterized by strong CXCL16 and CCL20 expression. This hypothesis was supported by the finding that the percentage of CXCR6 expressing ILCs was alleviated in blood of psoriatic patients. Together these data link a strong expression of CXCL16 to metabolic syndrome in psoriasis and indicate a possible link to ILC activation and tissue distribution in obese psoriatic patients. These data contribute to the understanding of the complex interaction of innate immunity and metabolic state in psoriasis.

Reduced expression of CXCL16/CXCR6 is involved in the pathogenesis of hidradenitis suppurativa

“…The CXCL16‐CXCR6 axis could also regulate the topography of innate lymphoid cells (ILCs). Trapping of CXCR6 + ILCs in the skin and adipose tissue, as well as their alleviation in blood, were observed in psoriasis patients, especially ILC1 and ILC3 subsets 35 . CXCL16‐CXCR6 crosstalk could coordinate the interleukin (IL)‐22 producing ILC3s for intestinal mucosal defense, and IL‐22 production from ILCs was correlated with CXCR6 expression 36 .…”

Understanding Type 3 Innate Lymphoid Cells and Crosstalk with the Microbiota: A Skin Connection

“…Furthermore, psoriasis occurs more frequently in obese individuals, suggesting systemic metabolic involvement in the disease state [108]. In these individuals, monocytes and skin cells have elevated CXCL16 expression, and ILC3s in psoriasis patients have enhanced expression of the CXCL16 receptor, CXCR6 [108]. Proinflammatory ILCs migrate to the skin and promote psoriatic inflammation through CXCL16-CXCR6 interaction [108].…”

“…In these individuals, monocytes and skin cells have elevated CXCL16 expression, and ILC3s in psoriasis patients have enhanced expression of the CXCL16 receptor, CXCR6 [108]. Proinflammatory ILCs migrate to the skin and promote psoriatic inflammation through CXCL16-CXCR6 interaction [108]. The many roles of ILC3s in psoriasis hence demonstrate their significance in orchestrating skin immunity.…”