No impairment of monocyte‐derived Langerhans cell phenotype or function in early‐onset psoriasis

Abstract

BackgroundMigration of epidermal Langerhans cells (LCs) in response to the cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α is impaired in uninvolved skin of patients with early-onset psoriasis.AimTo investigate whether this impairment is a reflection of a systemic defect in dendritic cells (DCs), using an established model of monocyte-derived LC-like cells (mLCs).MethodsCD14+ monocytes isolated from both patients with psoriasis and healthy control volunteers were cultured in a cytokine cocktail for 5 days to promote their differentiation into mLCs, then stimulated for 24 h with TNF-α, IL-1β (both 100 ng/mL) or medium alone. Cellular surface protein expression was quantified by flow cytometry, and the ability of cells to migrate to media supplemented with C-C motif ligand (CCL)19 was assessed using a Transwell migration assay. The cytokine and chemokine content of supernatants was analysed by cytokine array.ResultsCD14+ cells acquired an LC-like phenotype with high expression of CD1a and major histocompatibility complex (MHC) class II. There were no differences in the expression of activation markers or in the secretion of cytokines by mLCs isolated from patients with psoriasis and those isolated from healthy controls. Moreover, mLCs isolated from both groups displayed comparable ability to migrate in vitro.ConclusionsThese data suggest that the failure of LCs to migrate in response to stimulation in patients with psoriasis is not attributable to a systemic defect in DC function, but is rather a reflection of local changes in the epidermal microenvironment.

Impaired Langerhans cell migration in psoriasis is due to an altered keratinocyte phenotype induced by interleukin-17

“…Our current findings suggest that KCs play an important role, and may be solely responsible, for the impaired LC migration observed in the PN skin in chronic plaque psoriasis. Our previous studies have shown that there is no obvious impairment of blood monocyte‐derived LCs . The implication is rather that impairment of LC migration is associated with an altered epidermal phenotype.…”

“…Our previous studies have shown that there is no obvious impairment of blood monocyte-derived LCs. 16 The implication is rather that impairment of LC migration is associated with an altered epidermal phenotype. The data presented here are consistent with that view.…”

Does psychosocial stress play a role in the exacerbation of psoriasis?

“…Studies have shown that LC migration is abnormal in psoriasis; migration is impaired following exposure to contact allergens, IL-1b or tumour necrosis factor-a, 57 stimuli that would induce migration in normal skin. 58 This effect is thought to be due to an alteration in the epidermal microenvironment, 59 rather than a systemic change in the function of the dendritic cells. Kleyn et al 56 observed in healthy volunteers that LC migration from the epidermis (identified by a reduced frequency of epidermal LCs) is triggered by acute psychological stress (Trier paradigm).…”

Guttate psoriasis is associated with an intermediate phenotype of impaired Langerhans cell migration

“…Langerhans cells (LC), a population of epidermal dendritic cells that present antigens to T lymphocytes and orchestrate cutaneous immune responses, have been implicated in the pathogenesis of psoriasis . In normal skin the mobilization of LC requires signals from interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α.…”

“…In previous investigations we have shown that early‐onset (presenting before age 40 years) chronic plaque psoriasis (CPP) is associated with a substantial inhibition of LC migration in response to IL‐1β and TNF‐α . The view is that the impairment of LC mobilization is the consequence of abnormalities in the epidermal microenvironment …”