Interleukin-33: Its Emerging Role in Allergic Diseases

Ding, Wen; Zou, Gui-Lin; Zhang, Wei; Lai, Xing-Ning; Chen, Hou-Wen; Xiong, Likuan

doi:10.3390/molecules23071665

Cited by 58 publications

(58 citation statements)

References 110 publications

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“…IL‐33 is an epithelial‐derived cytokine and an essential mediator of type 2 inflammation, promoting bronchial hyperresponsiveness in AA. It is released to alert the immune system by first‐line cells, such as tissue epithelial cells, following exposure to exogenous stimuli, including allergens . Importantly, high levels of serum IL‐33 and IL‐33 receptor genetic polymorphism were found in patients with multiple sclerosis, suggesting a relevant role of this cytokine in the pathogenesis of autoimmune disorders .…”

Section: Discussionmentioning

confidence: 99%

Serum levels of epithelial‐derived mediators and interleukin‐4/interleukin‐13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma

Kalinauskaitė-Žukauskė

Janulaitytė

Januškevičius

et al. 2019

Scand J Immunol

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Allergens are the main trigger that enhances airway type 2 inflammation, and the epithelium is the first line of defense that reacts to its exposure. Therefore, epithelial‐derived mediators, such as interleukin (IL)‐25, IL‐33, thymic stromal lymphopoietin (TSLP) and ezrin, may play a role as alarmins in IL‐4/IL‐13 signaling in allergic asthma (AA). We investigated the serum levels of IL‐25, IL‐33, TSLP, ezrin, IL‐4 and IL‐13, after bronchial challenge with Dermatophagoides pteronyssinus in patients with AA. We examined 18 subjects: nine steroid‐free stable patients with AA sensitized to D. pteronyssinus and nine non‐atopic healthy subjects (HS). Bronchial allergen challenge was performed using inhaled D. pteronyssinus allergen. IL‐4, IL‐13, IL‐25, IL‐33, TSLP and ezrin levels in serum were measured by ELISA at two time points ‐ before and 24 hours after bronchial allergen challenge. The serum levels of IL‐25, TSLP and ezrin did not differ between AA and HS groups at baseline. However, after allergen exposure, significant increases in serum levels of IL‐25, TSLP and ezrin were observed only in patients with AA. The serum level of IL‐33 at baseline was significantly higher in the AA group compared with HS, but the allergen challenge did not provoke an increase of this cytokine in any group. IL‐4 and IL‐13 levels were significantly higher at baseline in the AA group compared with HS and, after allergen exposure, were significantly increased in the AA group, with no effect on HS. Thus, the epithelial‐derived mediators IL‐25, TSLP and ezrin, via IL4/IL13 signaling, enhance type 2 inflammation after bronchial challenge with D. pteronyssinus in AA.

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Section: Discussionmentioning

confidence: 99%

Serum levels of epithelial‐derived mediators and interleukin‐4/interleukin‐13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma

Kalinauskaitė-Žukauskė

Janulaitytė

Januškevičius

et al. 2019

Scand J Immunol

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“…IL‐1 ligands (IL‐18) is related with the clinical and histopathologic features of chronic AD lesions which may due to dysfunctional inflammasome processing . Recently, IL‐33, a newly described member of the IL‐1 family, has been found to play an important role in inducing Th2 immune responses and provide novel insights for addressing AD …”

Section: Discussionmentioning

confidence: 99%

“…26,27 Recently, IL-33, a newly described member of the IL-1 family, has been found to play an important role in inducing Th2 immune responses and provide novel insights for addressing AD. 28 Several mouse models of human AD have been developed that have provided insights into the pathogenesis of human AD. 17,18 Epicutaneous sensitization is a method which reveals characteristic clinical and histological features of AD.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model

Kao

Hsu

Lee

et al. 2020

The Kaohsiung J of Med Scie

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Atopic dermatitis (AD) is a chronic inflammatory skin disease and sometimes is a tough challenge for physicians. We previously reported that in Th2 environment, the production and secretion of thymic stromal lymphopoietin (TSLP) from human keratinocytes was inhibited by recombinant heat shock protein 70 (rHSP70). The present study assessed the therapeutic effectiveness of rHSP70 in a mouse model of AD. An experimental model of AD was reproduced by systemic sensitization and local epicutaneous challenge with ovalbumin (OVA). Treatment of rHSP70 was performed by subcutaneous administration. The levels of OVA‐specific IgE, as well as cytokines, were detected by ELISA. Skin samples from patch areas were also taken for histologic examination. Injection of rHSP70 improved the histologic picture by reducing the thickness of epidermis and allergic inflammation. Skin sonography revealed rHSP70 ameliorated skin remodeling. rHSP70 also significantly decreased the protein expression of TSLP of skin from patch areas. Furthermore, in ex vivo studies also showed group of rHSP70 treatment decreased IL‐13, RANTES, MIP‐1β and increased IFN‐γ secreted from splenocytes stimulated with OVA. The rHSP70 intervention in the mouse model of AD reduced the skin expression of TSLP and attenuated the clinical appearance of OVA‐induced AD mice. The effect was achieved by suppressed Th2 immune response in injected skin tissue and enhanced systemic Th1 immune response. These results suggest that rHSP70 have potential as a promising protein for the treatment of AD.

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“…Both S. epidermidis and S. aureus are well-known human pathogens that may cause serious opportunistic infections of the respiratory tract. However, Staphylococcus species are commonly detected in the normal micro ora of the skin, intestine, and upper airway and many studies implicate the role of Staphylococcus species as symbiotic commensal organisms that are also involved in allergic diseases [29][30][31]. Patients with allergic eczema are more likely to have skin colonized with S. aureus than healthy control subjects, and disease severity is associated with S. aureus colonization.…”

Section: Discussionmentioning

confidence: 99%

Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa

Jeon

Gil

Won

et al. 2020

Preprint

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Background: The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models.Results: Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. Conclusion: Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.

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Interleukin-33: Its Emerging Role in Allergic Diseases

Cited by 58 publications

References 110 publications

Serum levels of epithelial‐derived mediators and interleukin‐4/interleukin‐13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma

Serum levels of epithelial‐derived mediators and interleukin‐4/interleukin‐13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma

Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model

Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa

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