Role of neuroimmune circuits and pruritus in psoriasis

Abstract

Psoriasis is a chronic inflammatory skin disease presenting with an array of clinical phenotypes, often associated with pruritus. Environmental and psychological stressors can exacerbate psoriasis symptoms and provoke flares. Recent studies suggest a dysfunctional hypothalamic‐pituitary‐adrenal (HPA) axis in some patients with psoriasis that can result in immune dysregulation. The immune system, in turn, can communicate with the nervous system to induce, maintain or aggravate psoriasis. In the skin, peripheral sensory as well as autonomic nerves control release of inflammatory mediators from dendritic cells, mast cells, T cells or keratinocytes, thereby modulating inflammatory responses and, in case of sensory nerves, pruritus. In response to the environment or stress, cytokines, chemokines, proteases, and neuropeptides fluctuate in psoriasis and influence immune responses as well as nerve activity. Furthermore, immune cells communicate with sensory nerves which control release of cytokines, such as IL‐23, that are ultimately involved in psoriasis pathogenesis. Nerves also communicate with keratinocytes to induce epidermal proliferation. Notably, in contrast to recent years the debilitating problem of pruritus in psoriasis has been increasingly appreciated. Thus, investigating neuroimmune communication in psoriasis will not only expand our knowledge about the impact of sensory nerves in inflammation and pruritus and give new insights into the impact of environmental factors activating neuroimmune circuits or of stress in psoriasis, but may also lead to novel therapies. This review summarizes the relevant literature on the role of neuroimmune circuits, stress and how the central HPA axis and its peripheral equivalent in the skin, impact psoriasis.

Neurokinin 1 Receptor Antagonists for Pruritus

“…The pathogenesis of chronic pruritus is complex and can result from an underlying disease directly affecting the skin, i.e. atopic dermatitis, psoriasis, urticaria, epidermolysis bullosa or systemic diseases such as chronic liver disease, hyperthyroidism, lymphoma and neurological disease, to name a few [1,6,7]. Itch can also arise from unknown causes as well as from psychological disorders [1].…”

<p>IL-33/13 Axis and IL-4/31 Axis Play Distinct Roles in Inflammatory Process and Itch in Psoriasis and Atopic Dermatitis</p>

“…7,8 The mechanisms that may be involved in Ps and AD itch are complex and multifactorial, 9 however, the role of inflammation is likely to be significant since several inflammatory mediators elevated in both conditions are known to cause itch and anti-inflammatory treatments can reduce inflammatory signs as well as itch. 8,10 Interleukins are cytokines which play key roles in proinflammatory and anti-inflammatory signaling pathways. Interleukins 4, 13, 31 and 33 have been studied in multiple skin diseases including psoriasis and atopic dermatitis and targeted therapy for some of these interleukins are used for treatment of these conditions.…”

The nerve injuries interfere with the development of psoriasis

“…It is such bidirectional communication creates feedback loops in chronic in ammatory skin diseases. 23 There are increasing observations supporting the direct or indirect participation of the nerve in psoriasis development.…”

“…23,27,28 (4) Trigger factors of psoriasis can upregulate and activate some receptors and ion channels on sensory nerves, leading to neurogenic in ammation and pruritus in psoriasis. 23,29 (5) Several tentative therapies, including dermatiome-shaving, capsaicin cream, resiniferatoxin, onabotulinumtoxinA, and K252a (a higha nity nerve growth factor receptor blocker), can improve psoriasis or psoriasiform dermatitis, through reducing lesional nerve bers or sensory denervation. [30][31][32][33][34][35][36] And nerve blockade based on locoregional anaesthesia has been proposed in psoriasis treatment.…”

“…Th2 type IL-4, IL-5, and IL-13) can trigger the activation of sensory bers to coordinate host-protective behavioral responses. 23,29,44 It has been demonstrated that, based on transgenic KC-Tie2 mouse model of psoriasiform dermatitis, nervous interventions of surgical denervation, neuropeptide blocker, and botulinum neurotoxin A injection can signi cantly decrease IL-23, CD4 + T cells, especially CD11 + dendritic cells, along with the improvement of psoriatic acanthosis. 6,46 With wild-type mice, here we demonstrated here that unilateral denervation surgery remarkably decreased Th17 cell differentiation, TNF signaling, Toll-like receptor signaling, Th1 and Th2 cell differentiation, and JAK-STAT signaling pathways on ipsilateral side.…”