IL-33/Vitamin D Crosstalk in Psoriasis-Associated Osteoporosis.

Massimo De Martinis,Maria Maddalena Sirufo,Sebastiano Gangemi,Giovanni Pioggia,Lia Ginaldi,Enrica Maria Bassino,Francesca De Pietro

doi:10.3389/fimmu.2020.604055

Abstract

Patients with psoriasis (Pso) and, in particular, psoriatic arthritis (PsoA) have an increased risk of developing osteoporosis (OP). It has been shown that OP is among the more common pathologies associated with Pso, mainly due to the well-known osteopenizing conditions coexisting in these patients. Pso and OP share common risk factors, such as vitamin D deficiency and chronic inflammation. Interestingly, the interleukin (IL)-33/ST2 axis, together with vitamin D, is closely related to both Pso and OP. Vitamin D and the IL-33/ST2 signaling pathways are closely involved in bone remodeling, as well as in skin barrier pathophysiology. The production of anti-osteoclastogenic cytokines, e.g., IL-4 and IL-10, is promoted by IL-33 and vitamin D, which are stimulators of both regulatory and Th2 cells. IL-33, together with other Th2 cytokines, shifts osteoclast precursor differentiation towards macrophage and dendritic cells and inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis by regulating the expression of anti-osteoclastic genes. However, while the vitamin D protective functions in OP and Pso have been definitively ascertained, the overall effect of IL-33 on bone and skin homeostasis, because of its pleiotropic action, is still controversial. Emerging evidence suggests a functional link between vitamin D and the IL-33/ST2 axis, which acts through hormonal influences and immune-mediated effects, as well as cellular and metabolic functions. Based on the actions of vitamin D and IL-33 in Pso and OP, here, we hypothesize the role of their crosstalk in the pathogenesis of both these pathologies.

Highlights

Psoriasis (Pso) is a chronic autoimmune multifactorial disease that is associated with systemic inflammation
Patients suffering from Pso, Vitamin D/IL-33 Axis in Psoriasis and Osteoporosis those with psoriatic arthritis (PsoA) or more severe forms of the disease, develop multiple comorbidities in addition to joint diseases, including cardiovascular and rheumatologic disorders, infections, obesity, and diabetes [5,6,7]
The bone protective effect of IL-33 could be masked or prevented by concomitant factors characterizing Pso, such as the deficiency of vitamin D and the altered PTHmediated calcium–phosphorus metabolism, the prevalence of Th1/Th17 systemic inflammation with an increase in osteoclastogenic cytokines, and mechanisms of counterregulation of IL-33 signaling associated with the inflammatory process [99]

Summary

INTRODUCTION

Psoriasis (Pso) is a chronic autoimmune multifactorial disease that is associated with systemic inflammation It presents with skin erythematous plaques, covered by characteristic white silvery scales [1]. Patients suffering from Pso, Vitamin D/IL-33 Axis in Psoriasis and Osteoporosis those with psoriatic arthritis (PsoA) or more severe forms of the disease, develop multiple comorbidities in addition to joint diseases, including cardiovascular and rheumatologic disorders, infections, obesity, and diabetes [5,6,7]. The link between these comorbidities is likely systemic inflammation [8]. We hypothesize a mechanistic link between vitamin D and IL-33 in patients with Pso and associated OP

PATHOGENIC MECHANISMS LINKING PSO AND OP

THE ROLE OF VITAMIN D

CONCLUSIONS