Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis

Abstract

Epithelial cell-derived thymic stromal lymphopoietin (TSLP) is a master switch for asthma or atopic dermatitis by inducing a dendritic cell-mediated Th2-type allergic inflammation. Allergic rhinitis is also pathologically characterized by Th2-type allergic inflammation. This study demonstrates that mast cells regulate the epithelial TSLP expression in allergic rhinitis. TSLP expression was found to be up-regulated predominantly in the nasal epithelium in the ovalbumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis, which was abolished in mast cell-deficient WBB6F1-W/W v in comparison with control WBB6F1-+/+ mice. Similarly, the epithelial TSLP expression was reduced in Fc receptor c chain (FccR)-deficient mice, where the high-affinity IgE receptor (FceRI) is not expressed on mast cells, in comparison with control C57BL/6 mice. Furthermore, the administration of neutralizing TSLP antibody during the challenge phase of OVA inhibited the development of allergic rhinitis. These results suggest that the direct stimulation of epithelial cells by antigens alone may not be sufficient to induce TSLP expression in the nasal epithelium, and that mast cell regulation of epithelial TSLP expression, possibly via FceRI, plays an important role in the development of allergic rhinitis. Key words: Allergic rhinitis Á Epithelial cells Á Mast cells Á TSLP IntroductionThymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which binds to a TSLP receptor (TSLPR) consisting of the IL-7 receptor a-chain (IL-7Ra) and a common c receptor-like chain (TSLPR-c) [1,2]. TSLP was originally identified as a factor derived from a thymic stromal cell line that could support the growth of a mouse B cell line [3]. However, recently, TSLP, derived from epithelial cells, has been shown to be capable of activating CD11c + myeloid DC to up-regulate costimulatory molecules, leading to the differentiation of CD4 + T cells into Th2 cells. Therefore, it plays a key role in the development of allergic diseases such as asthma or atopic dermatitis [1,2,4]. For instance, transgenic mice expressing TSLP in keratinocytes or in lung epithelial cells have been shown to develop atopic dermatitis-or asthma-like inflammation in the skin or the lung, respectively, while TSLPR null mice failed to develop an inflammatory lung response to inhaled antigen [5][6][7]. In humans, TSLP has been shown to be expressed by keratinocytes in atopic dermatitis and by bronchial epithelial cells in asthmatic airways [8,9].In contrast to the pro-allergic action of TSLP, regulation of TSLP expression in epithelial cells has not been fully elucidated. Previous studies suggest that TSLP expression in mouse keratinocytes is regulated by vitamin D and retinoic acid signaling [10] [17]. In addition, mast cells up-regulate the production of a variety of cytokines/chemokines in epithelial cells and fibroblasts, and induce the recruitment of basophils, T cells, and eosinophils into sites of allergic inflammation as well as their own intraepithelial accumulation....

Inhibition of IL-32 and TSLP production through the attenuation of caspase-1 activation in an animal model of allergic rhinitis by Naju Jjok (Polygonum tinctorium)

“…TSLP is expressed in the nasal mucosa of mice with AR (25) and is produced in activated mast cells (26). In our study, mice administered NJJ showed significantly decreased levels of TSLP in serum and nasal mucosal tissue ( Fig.…”

Regulation of type 2 immunity to helminths by mast cells

“…Indeed in line with our findings it was previously reported that induction of TSLP in airway epithelial cells is abolished in mice lacking MCs during allergic rhinitis. 31 MCs are able to produce a plethora of mediators upon their activation (reviewed in ref. 10).…”

Thymic stromal lymphopoietin is a critical mediator of IL‐13‐driven allergic inflammation

“…For some experiments, rat anti-mouse TSLP neutralizing Ab (R&D Systems) or control rat IgG2a (15 mg/kg per mouse; Santa Cruz Biotechnology, Santa Cruz, CA, USA) were administered intraperitoneally 24 h before the first IL-13 challenge. The dosage of the Ab (15 mg/kg) was chosen based on previous experiments [30,31].…”

“…The number of Hansel-positive eosinophils in the nasal mucosa or the number of PAS-positive goblet cells in the total nasal epithelial lining of the coronal sections was counted microscopically in a blinded manner and it was expressed as the number per total length of the total nasal epithelial lining of the coronal sections (the number/mm) as previously described [31]. Two or four specimens of the Hansel-or PAS-stained coronal sections from one mouse were selected.…”