Correlation between IL-36α and IL-17 and Activity of the Disease in Selected Autoimmune Blistering Diseases

Abstract

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury.

Upregulation of IL‐36 cytokines in folliculitis and eosinophilic pustular folliculitis

“…Similar to folliculitis, high expression of IL‐36β, IL‐36γ and IL‐36Ra was detected in the follicular epithelium and epidermis in EPF compared with the levels in normal skin. IL‐36α serum concentrations were significantly high in bullous pemphigoid, which is characterised by eosinophilic infiltration . In parallel with this, the immunohistological expression of IL‐36α was significantly higher in EPF than in folliculitis and normal follicles in the present study.…”

“…IL-36a serum concentrations were significantly high in bullous pemphigoid, which is characterised by eosinophilic infiltration. 12 In parallel Figure 6 Correlations between IL-36b and IL-36Ra (a, c and e) and between IL-36c and IL-36Ra (b, d and f) in the follicular epithelium. In normal follicles, there were negative correlations between IL-36b and IL-36Ra and between IL-36c and IL-36Ra (a and b).…”

“…9,10 One of the major biological functions of IL-36a, IL-36b and IL-36c is their potent neutrophilic and eosinophilic chemoattraction. 4,11 Therefore, the overexpression of IL-36s has been documented in various skin diseases such as allergic contact dermatitis, 12 atopic dermatitis, mycosis fungoides, S ezary syndrome, 13 autoimmune blistering diseases, 11 hidradenitis suppurativa and acne. 14 Eosinophilic pustular folliculitis (EPF) is a distinct clinical entity first described in 1965 by Ise and Ofuji as a variant of superficial pustular dermatosis.…”

IL‐17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art

“…Th17 cells and IL‐17 have also been identified to be implicated in the pathogenesis of several human autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, systemic sclerosis, primary Sjogren's syndrome, alopecia areata, and vitiligo . Furthermore, a recent study reported a correlation between the serum levels of IL‐17 and activity of the disease in selected autoimmune bullous skin diseases, such as dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) …”

From bench to bedside: evolving therapeutic targets in autoimmune blistering disease

“…Generated from Th17 cells, subset of T helper cells, IL‐17, induces expression of cytokines and chemokines (IL‐1β, GM‐CSF, G‐CSF, CXCL1, CXCL2) and MMP‐9 that facilitate granulocyte recruitment, activation and ultimately protease release that results in characteristic BMZ degradation . IL‐17 is elevated in BP patients’ serum and blister fluid and has been implicated in mediating tissue destruction . Recent experimental studies have identified that mouse models deficient in IL‐17a do not develop BP .…”