The Role of Intereukin-31 in Pathogenesis of Itch and Its Intensity in a Course of Bullous Pemphigoid and Dermatitis Herpetiformis

Kulczycka-Siennicka, Lilianna; Cynkier, Anna; Waszczykowska, Elżbieta; Woźniacka, Anna; Żebrowska, Agnieszka

doi:10.1155/2017/5965492

Cited by 29 publications

(28 citation statements)

References 23 publications

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“…It is, however, as yet unclear whether BP patients display elevated serum levels of IL-31, since the currently published literature has reported conflicting observations. Our own investigation showed only minor elevations in serum IL-31 levels vs. non-BP controls (51) compared to Salz et al (50), who observed significant increases, and Kulczycka-Siennicka et al (52), who reported reduced levels of the cytokine. Despite these different observations regarding IL-31 serum levels, it is clear that eosinophils are one of the major sources for the increased IL-31 levels in BP blister fluids, which often contain a highly enriched accumulation of eosinophils.…”

Section: Il-31 In Autoimmune Skin Diseasescontrasting

confidence: 46%

Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases

2019

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Many autoimmune skin diseases, such as bullous pemphigoid (BP), psoriasis and certain types of chronic urticaria, are associated with intensive pruritus. While histamine and neuropeptides have previously been ascribed to play a role in itch that accompanies these diseases, recent evidence suggests that the pruritogenic cytokine interleukin (IL)-31 is a major driver of pruritic responses. IL-31 was originally shown to be produced by activated helper T cells, particularly Th2 cells, mast cells, macrophages and dendritic cells. However, more recent evidence demonstrated that eosinophils are a major source of this cytokine too, particularly in bullous pemphigoid. Basophils have also been shown to express the cytokine which, through autocrine action, strongly supports the production of other Th2-type cytokines from these cells. These investigations suggest that the dynamic recruitment of eosinophils and basophils in some autoimmune skin diseases could play an important role in the severity of IL-31-mediated itch. Furthermore, these studies suggest that IL-31, in addition to its pruritic actions, also has potential immunomodulatory roles in terms of supporting Th2-type immunity, which often underpins IgE-associated autoimmune diseases (such as bullous pemphigoid and urticaria) as well as allergies. While the role of IL-31 in psoriasis remains to be clarified, current evidence shows that this cytokine plays a major role in BP, chronic spontaneous urticaria and dermatomyositis. This suggests potential use of IL-31 receptor-blocking therapeutic approaches (e.g., Nemolizumab) for the treatment of IL-31-associated disorders.

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Section: Il-31 In Autoimmune Skin Diseasescontrasting

confidence: 46%

Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases

2019

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“…At present there are conflicting reports regarding relative IL-31 levels in BP sera compared with healthy controls. Kulczycka-Siennicka et al (29) reported reduced levels of IL-31 in BP sera, whereas a recent study by Salz et al (30), which was published at the time our current work was first submitted, reported significant increases. Salz et al (30) also observed high levels of IL-31 in BP blister fluids, as well as an association with granulocytes (30), which we can confirm, although our study demonstrates for the first time that eosinophils are the main source of this cytokine.…”

Section: Discussionmentioning

confidence: 56%

Eosinophils are a Major Source of Interleukin-31 in Bullous Pemphigoid

Rüdrich¹,

Gehring²,

Παπακωνσταντίνου³

et al. 2018

Acta Derm Venerol

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Bullous pemphigoid (BP) is characterized by substantial skin and blood eosinophilia as well as intensive pruritus. Since the pruritogenic cytokine interleukin (IL)-31 is increased in inflammatory skin diseases the aim of this study was to determine whether IL-31 plays a role in BP. Using immunofluorescence, IL-31 expression was analysed in eosinophils derived from blister fluids and skin from patients with BP and IL-31 levels in blister fluids, serum and culture supernatants were determined by enzyme-linked immunoassay (ELISA). High levels of IL-31 expression were observed in BP blister fluids, but they were only marginally elevated in BP serum compared with healthy controls. Eosinophils from either BP blister fluids or skin biopsies showed strong expression of IL-31. Furthermore, peripheral blood eosinophils from patients with BP, but not healthy controls, released high levels of IL-31, reflecting those in blister fluids. In conclusion, eosinophils are a major source of IL-31 in BP and this cytokine may contribute to itch in patients with BP.

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“…We have previously shown that Th2 type cytokines are also elevated in the skin of DH patients, thereby allowing speculation about a possible role of IL-31 in the associated pruritus. Interestingly, while a previous paper did not show significant elevation of serum IL-31 concentration in DH patients (152), a recent study by our group demonstrated that IL-31 was not only elevated in DH serum, but also significantly over-expressed in the skin, where it co-localized with IL-31RA (153).…”

Section: Pathogenesismentioning

confidence: 57%

Dermatitis Herpetiformis: Novel Perspectives

et al. 2019

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Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.

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The Role of Intereukin-31 in Pathogenesis of Itch and Its Intensity in a Course of Bullous Pemphigoid and Dermatitis Herpetiformis

Cited by 29 publications

References 23 publications

Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases

Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases

Eosinophils are a Major Source of Interleukin-31 in Bullous Pemphigoid

Dermatitis Herpetiformis: Novel Perspectives

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