Transcriptional analysis of the <scp>IL</scp>‐33 receptor suppression of tumourigenicity 2 and its effects on canine Type 2 T helper cells: a preliminary study

Background -The involvement of interleukin (IL)-33 produced by keratinocytes has been suggested in the pathogenesis of canine atopic dermatitis (cAD). House dust mite (HDM)-derived proteases induce the production of various cytokines and chemokines in keratinocytes via protease-activated receptor-2 (PAR-2); however, their effects on IL-33 mRNA expression in canine keratinocytes have not been determined.Hypothesis/Objective -To clarify whether HDM-derived proteases induce IL-33 mRNA expression in canine keratinocytes via PAR-2.Methods and materials -Expression of IL-33 mRNA was quantified by real-time PCR in a cell line of canine progenitor epidermal keratinocytes (CPEK) stimulated with Dermatophagoides farinae (Der f) whole body extract, Der f pre-treated with cysteine protease and serine protease inhibitors, and trypsin. Trypsin and Der f-mediated IL-33 mRNA expression also was measured in CPEK cells treated with a PAR-2 antagonist.Results -Der f enhanced IL-33 mRNA expression in CPEK cells in incubation time-and dose-dependent manners. Der f pre-treated with a serine protease inhibitor, and not a cysteine protease inhibitor, abrogated an increase in IL-33 mRNA expression in CPEK cells. Trypsin also enhanced IL-33 mRNA expression in CPEK cells. Trypsin-mediated IL-33 mRNA expression was completely abolished by a PAR-2 antagonist, while Der fmediated IL-33 mRNA expression was partially and significantly diminished by it.Conclusions and clinical relevance -Der f-derived serine protease upregulated IL-33 mRNA expression in CPEK cells at least in part via PAR-2. These findings suggest that HDM may be involved in the development of C AD by increasing IL-33 mRNA expression in keratinocytes.

Section: Introductionmentioning

confidence: 54%

“…2 IL-33 also was shown to enhance IL-5 and IL-13 mRNA transcriptions in canine Th2 cells. 3 These findings suggest that IL-33 produced by keratinocytes is involved in the pathogenesis of cAD. However, it remains unclear what factors have the potential to induce or increase IL-33 mRNA expression in canine keratinocytes.…”

Section: Introductionmentioning

confidence: 86%

House dust mite‐derived serine protease upregulates gene expression of interleukin‐33 in canine keratinocytes via protease‐activated receptor‐2

Nishimura

Miyajima

Takahashi

et al. 2021

“…67 Suppression of tumorigenicity 2 (ST2), a receptor for IL-33, was expressed on canine Th2 cells, and stimulation of cells with IL-33 led to the expression of type 2 cytokines. 68 Furthermore, significant upregulation of IL-33 was found in chronic lesional skin of canine AD. 69 Although GATA3 + ILC2-like cells were not increased in the peripheral blood of AD dogs, 59 further work should evaluate ST2 + or TSLPR + ILC2 in atopic skin of dogs.…”

Section: Innate Immunity In Admentioning

confidence: 96%

“…The expression of TSLP was enhanced in an in vitro culture of canine keratinocytes after exposure to toll‐like receptor 1 or 2 ligand 67 . Suppression of tumorigenicity 2 (ST2), a receptor for IL‐33, was expressed on canine Th2 cells, and stimulation of cells with IL‐33 led to the expression of type 2 cytokines 68 . Furthermore, significant upregulation of IL‐33 was found in chronic lesional skin of canine AD 69 .…”

Section: Innate Immunity In Admentioning

confidence: 99%

Epithelial–immune crosstalk with the skin microbiota in homeostasis and atopic dermatitis – a mini review

Kobayashi

Imanishi

2021

The skin is a complex and dynamic ecosystem, wherein epithelial cells, immune cells and the skin microbiota actively interact and maintain barrier integrity and functional immunity. Skin microbes actively tune the functions of the resident immune cells. Dysbiosis – alterations in the resident microbiota – leads to the dysregulation of host immunity. Microbiome analyses in humans and dogs with atopic dermatitis (AD) have shown shifts in microbial diversity, and in particular, an increased proportion of staphylococci. Monogenic diseases that manifest AD‐like symptoms provide insights into the pathogenesis of AD and the mechanisms of dysbiosis, from both the epithelial and immunological perspectives. The symbiotic relationships between the host and microbiota must be maintained constitutively. Detailed mechanisms of how host immunity regulates commensal bacteria in the steady state have been reported. The skin harbours multiple tissue‐resident immune cells, including both innate and adaptive immune cells. Recent studies have highlighted the fundamental role of innate lymphoid cells (ILCs) in the maintenance of barrier functions and tissue homeostasis. ILCs directly respond to tissue‐derived signals and are instrumental in barrier immunity. Epithelial cells produce alarmins such as thymic stromal lymphopoietin (TSLP) and interleukins (IL)‐33 and IL‐25, all of which activate group 2 ILCs (ILC2s), which produce type 2 cytokines, such as IL‐5 and IL‐13, boosting type 2 immune reactions. Dysregulation of the epithelial–ILC crosstalk results in allergic inflammation. This review highlights our understanding of the active interactions between the host epithelial and immune cells, and microbiota, providing a foundation for novel therapeutic strategies for inflammatory skin diseases.

“…In dogs, one study reported that IL‐33 enhanced the transcription of il‐5 and il‐13 in Th2 cells . In the present study, we investigated the transcription and expression of IL‐33 in chronic lesional skin of cAD in order to demonstrate a relationship with immunopathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Expression of IL‐33 in chronic lesional skin of canine atopic dermatitis

Asahina

Nishida

Kamishina

et al. 2018

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