Depression and Obesity in Patients With Psoriasis and Psoriatic Arthritis: Is IL-17-Mediated Immune Dysregulation the Connecting Link?

Abstract

Patients with psoriasis are frequently obese and experience anxiety or suffer from depressive disorders. The immunopathogenesis of psoriasis and indeed psoriatic arthritis is largely based on the pivotal role of IL-17/IL-23 axis, to an extent that currently monoclonal antibodies selectively inhibiting IL-17 or IL-23 are routinely used for the treatment of psoriatic diseases. Emerging data, demonstrating a decisive role for IL-17 and IL-17 producing cell subsets, such as Th17 in the induction and progression of obesity and depression has led authors to suggest that psoriatic disease, obesity and anxiety/depression may indeed be interconnected manifestation of a state of immunedysregulation, the linked being IL-17 and its related cells. We discuss this hypothetical link in depth taking into account the beneficial effects anti-IL17 and anti-IL-17 receptor inhibitors in treating psoriatic disease and the on-going debate as to whether these biologics may exert a direct or indirect effect in ameliorating concomitant obesity and depressive disorders, which are frequently noted in the same patient.

Keywords: IL-17; IL-23; depression; immunity; obesity; psoriasis; psoriatic disease.

Figure 1

An-IL-17-mediated hypothesis of depressive disorder in an experimental model. In a young adult depression mouse model exposed to cumulative mild stress (CPMS) characterized by microglial activation, IL-17 in brain and blood, as well Th-17 cells are elevated. A hypothesis based on the assumption that microglia activation is pivotal for the increase of pro-inflammatory cytokines such as IL-16 and TGF-b, which polarize CD4+ T cells towards Th-17 is formulated. Experimental data suggest that anti-IL-17 mAb treatment, diminishes IL-17 induction and Th-17 differentiation and ameliorates anxiety and depression-like behaviors (61) (prepared with BioRender).

Figure 2

The hypothesis of immunedysregulation in obese depressed patients with psoriatic disease. An inflammatory response mediated by IL-17 producing cells such as Th17 is playing a pivotal role in the development of obesity, depression and psoriasis, in isolation or in combination. Immundysregulation manifested as increased expression of IL-17 and IL-17 producing cell subsets and diminished expression of regulatory cells (Tregs) and related cytokines (such as IL-10) is driving complex reactions leading to the development and progression of psoriatic disease and concomitant anxiety, depression and obesity. Those manifestations can partially be attributed to the inflammatory milieu, which fosters consistent inflammation, keratinocyte activation, cellular damage and skin destruction, as well as interconnected depressive disorders and weight gain. This vicious circle is stopped by IL-17 selective inhibitors, which can lead to the remission of skin lesions (and in the remission of arthritogenic features in the case of psoriatic arthritis or axial spondylarthritis) (prepared with BioRender).