[ZKKL] Academic Presentation | Recent Advances in the Role of IL‑33 in Autoimmune and Allergic Skin Diseases

2. 1 IL-33 The relationship with allergic diseases

2. 1. 1  Atopic dermatitis ( Atopic dermatitis ， AD) AD is a chronic inflammatory disease. The classic… February Type cytokines such as IL-4，IL-5， IL-13 In AD It is expressed in the acute-phase skin lesions of patients, whereas in the chronic phase it is predominantly… Th1 Produced by cells IFN- gamma. IL-33 Is IL-1 A new member of the family, and with… February It is associated with cell-mediated immune responses. It is predominantly expressed in barrier tissues such as the skin, small intestine, and lungs, where it can activate… February Produced by cells, mast cells, and eosinophils. February Type cytokines. Recent studies have shown that IL-33 Yes AD a warning sign, in the patient’s skin lesions IL-33 Expression levels are elevated. Recombinant… IL-33 After injection into mouse skin, it leads to T Cellular, macrophage, and eosinophilic infiltration, while simultaneously stimulating February Cytokine release, indicating that IL-33 In February An important role in cell-mediated immune responses. Compared with healthy individuals, AD In the patient's serum IL-33 The level was significantly elevated and positively correlated with the severity score of the patients’ skin lesions. Erythema, papules, crusts, scratch marks, and lichenification were… AD Common in patients 5  Lesion-like, IL-33 It is correlated with scratch marks and dryness scores. Following topical application of calcineurin inhibitors such as tacrolimus, patients exhibited a significant reduction in the severity of skin lesions, and in serum… IL-33 The level has decreased. Indicates that IL-33 With and AD It is related to the pathogenesis; mechanical injury and impaired skin barrier function can lead to alterations in keratinocytes, endothelial cells, and fibroblasts. IL-33 Increased expression, in the serum IL-33 The level might be AD A prognostic indicator of the severity of the patient’s condition.

2. 1. 2  Chronic urticaria Chronic urticaria is a common skin disorder, and numerous cytokines are involved in its pathogenesis. Studies have shown that IL‑33 expression is significantly upregulated in lesional skin compared with both healthy skin and non‑lesional skin. In China, some researchers have examined serum levels before and after treatment in patients with chronic urticaria. IL-33 Testing revealed that in patients with chronic urticaria, the serum… IL-33 The level was significantly elevated and showed a positive correlation with the severity of the patient’s condition. Loratadine treatment. 4  Patient serum one week later IL-33 The level has not shown any significant decline, suggesting it remains persistently high. IL-33 This may be one of the reasons why chronic urticaria patients are prone to relapse after discontinuing antihistamines.

2. 1. 3  Allergic purpura Henoch–Schönlein purpura is the most common form of IgA‑associated immune complex‑mediated vasculitis, but its molecular pathogenesis remains unclear. Chen T Once it is found that, during the active phase of patients with allergic purpura, the serum… IL-33 The level was significantly higher than during the recovery phase and correlated with the severity of the patient’s illness and serum levels of… Ig A Associated with anti‑endothelial cell antibodies. They hypothesize that in the serum of patients with Henoch–Schönlein purpura, IL-33 It is elevated and associated with the production of IgA antibodies in its pathogenesis.

2. 2 IL-33 The relationship with autoimmune diseases

2. 2. 1  Systemic lupus erythematosus ( Systemic lupus erythematosus ， SLE) Systemic lupus erythematosus

It is a complex, chronic inflammatory autoimmune disease that leads to damage in multiple tissues and organs. Cytokine-mediated immunity plays a role. SLE and the onset of other autoimmune diseases. IL-33 It is a pro-inflammatory cytokine, and in SLE It is considered the primary effector molecule among patients. Some studies have indicated that in… SLE In the patient's serum IL-33 The level has risen, and with SLE The severity of the patient’s illness is associated with renal damage. Meanwhile, Mok It is considered that, compared with the normal group, during the acute phase… SLE Soluble receptors in the patient’s serum ST2 It is elevated and positively correlated with the severity of the patient’s condition, and it is relatively sensitive to treatment response. It may serve as a potential biomarker for assessing disease severity. In… SLE In the patient's serum C R P ， ES R, Ig A With and IL-33 Closely related. As is well known, C R P ， ES An elevated R level indicates SLE The patient is in the acute inflammatory phase, as indicated by the study results. IL-33 It is associated with the acute inflammatory phase in patients with SLE.

2. 2. 2  Systemic sclerosis ( Systemic sclero-sis ， SSc) SSc is a systemic connective tissue disease characterized primarily by skin and visceral organ fibrosis, mainly caused by… February Cell-mediated autoimmune diseases. Manetti Wait for... SSc middle IL-33 and receptor ST2 The role was studied, and it was found that IL-33 and ST2 In SSc An exception was thrown in the middle. Subsequently, Yanaba Upon finding that, compared with the healthy control group, SSc In the patient's serum IL-33 The level is elevated, and in patients with diffuse cutaneous sclerosis, the serum contains… IL-33 The level is higher than that in patients with localized cutaneous sclerosis. Meanwhile, pulmonary fibrosis is also present in the serum. IL-33 It occurs in patients with elevated levels. This indicates that IL-33 may be involved in SSc The onset of the disease.

2. 2. 3  Common Pemphigus ( Pemphigus vlu-garis ， PV) PV is caused by anti-desmoglein antibodies. 3 and (  or )  Anti-desmoglein 1  Acquired autoantibody-mediated acantholysis, affecting the skin and… (  or )  An autoimmune blistering disease characterized primarily by mucosal blisters and erosions. Photovoltaic The precise molecular mechanisms underlying the onset of the disease remain unclear, and dysregulation of cytokine signaling may be involved. Photovoltaic The patient developed symptoms. IL-33 and soluble ST2 It plays an important role in the regulation of inflammation; however, its overexpression may contribute to the development of autoimmune diseases. Some researchers have investigated… IL-33 and ST2 In Photovoltaic to investigate its role in patients and explore its presence in their serum. IL-33 The relationship between the level and the patient’s clinical severity as well as the dose of hormone therapy. They found that Photovoltaic Serum IL-33 levels were significantly elevated in patients and were positively correlated with disease severity. Lesion area 1mg/kg/day In the serum of patients treated with prednisone IL-33 The level is less than 1 mg/kg/day The treatment efficacy is high. With ongoing therapy, the patients’ skin lesions have improved. IL-33 The level has declined. Indicates IL-33 May participate Photovoltaic Its occurrence is associated with the severity of the patient’s condition. Patients with extensive skin involvement exhibit a higher incidence compared to those with limited involvement. IL-33 A higher level indicates that it can reflect the severity of inflammation. It is believed that IL-33 It may be through induction. IL-6，TNF- The generation of α promotes February Cell activation, participation in Photovoltaic The onset of the condition influences the severity of the disease.