Interleukin-31 promotes helper T cell type-2 inflammation in children with allergic rhinitis

Abstract

Background: Interleukin-31 (IL-31) is a recently described cytokine that is involved in helper T cell type-2 (Th2)-mediated diseases. However, its regulatory effect in the pathogenesis of children allergic rhinitis (AR) needs to be further characterized. This study sought to evaluate the expression and role of IL-31 in children with AR. Methods: Sixty children with AR and 20 normal controls were included. IL-31 and Th2 cytokines production in tissue, serum, and nasal lavage was examined by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay, respectively. Peripheral blood mononuclear cells (PBMCs) were purified for in vitro regulation experiment of IL-31. Nasal epithelial cells (NECs) were cultured and stimulated by recombinant IL-31. results: The IL-31 mRNA and protein levels in both serum and nasal lavage were significantly enhanced in AR compared with normal controls, especially in children with asthma. The nasal IL-31 was associated with enhanced local Th2 cytokines and mucin 5AC (MUC5AC) expression. In vitro study showed that IL-31 promotes Th2 cytokines expression and MUC5AC upregulation and thus amplified Th2 inflammation. conclusion: Our results demonstrate that IL-31 expression in AR aggravated and amplified Th2 inflammation as well as mucin production, and provide a possible explanation for IL-31's regulatory role in the pathogenesis of AR. a llergic rhinitis (AR) is a common nasal disease and affects 10-40% of children with increasing prevalence (1,2). AR frequently coexists with asthma (most studies report a rate of 50-60%) in children (3). The major histological features of AR include helper T cell type-2 (Th2) inflammation accompanied by infiltration with eosinophils, allergen-specific IgE production, and thickening of the basement membrane (4,5). Activation of Th2 cells and further released cytokines induced accumulation of inflammatory cells, such as B cells, plasma cells, eosinophils, basophils, and neutrophils, which contributed to the occurrence of AR (6). Despite involvement of Th2 inflammation in AR was clearly clarified, its regulation was not fully understood.Interleukin-31 (IL-31) is a newly discovered four-helix bundle cytokine and expressed by several types of cells under both normal and disease state, such as activated CD4 + T cells, mast cells, monocytes, macrophages, immature and mature monocyte-derived dendritic cells and so on (7). The receptor of IL-31 consists of IL-31 receptor A (IL-31RA) and the oncostatin M receptor that is constitutively expressed on epithelial cells (8). The role of IL-31 in allergic diseases mainly focused on atopic dermatitis. Stephan et al. reported elevated IL-31 expression in atopic dermatitis (9). UIrike et al. found a correlation of Th2 cytokines with increased level of IL-31 in children with extrinsic atopic dermatitis (10). However, studies on respiratory allergic diseases are relatively few. Recently, Lei et al. (11) reported that high IL-31 level in asthmatic subjects, suggesting that IL-31 ...

Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

“…IL31 was previously shown to regulate cytokine production by airway epithelial cells 53 , and to be promoted by IL4, driving Th2 type inflammation 54 . Previous studies also indicated increased expression of IL31 in allergic asthma and allergic rhinitis 36,55 . As such, the regulation of IL31 may in part explain the Th2 skewing we observed in the WNT5A transgenic mouse and support a potential role for WNT5A in Th2 type inflammation and allergic asthma.…”

IL-31: A new key player in dermatology and beyond

“…Increased IL-31 protein and mRNA levels have been shown both in patients with allergic asthma and those with rhinitis (Table I). [72][73][74] IL-31 single nucleotide polymorphisms were significantly correlated with serum IgE levels in asthmatic patients. 75 Among patients with asthma/rhinitis with positive specific IgE levels, patients with dust mite and mugwort allergy had higher IL-31 levels.…”

“…72 Increased local secretion of T H 2 cytokines and mucin production have been reported in patients with allergic rhinitis after induction with IL-31. 74 Therefore the IL-31 pathway might be a potential target in the treatment of allergic asthma and rhinitis.…”

Oncostatin M and interleukin-31: Cytokines, receptors, signal transduction and physiology

“…However, recent studies imply that IL-31 might also be involved in allergic asthma and rhinitis [150][151][152], in inflammatory bowel disease [144] and malignancies of hematopoietic and lymphoid tissues [119,134,153]. Recent reviews summarize these findings in detail [123,124,154].…”