Epicutaneous Sensitization with Protein Antigen Induces Th9 Cells

Lin, Jingyi; Chen, Jau-Shiuh; Hsu, Chih-Chieh; Miaw, Shi‐Chuen; Liu, Ching-Yi; Lee, Shu-Jen; Chen, Pei–Chun; Wang, Li-Fang

doi:10.1038/jid.2011.382

Cited by 9 publications

(7 citation statements)

References 10 publications

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“…In cytokine gene targeted mice, IFN-γ as well as IL-4 are necessary for sensitization and elicitation, suggesting both Th1 and Th2 lymphocytes play a role in murine ACD ( Campos et al , 2003 ; Saulnier et al , 1995 ; Xu et al , 1996 ). Previous studies of protein contact dermatitis in a mouse model demonstrated that Th9 lymphocytes are detectable in the afferent phase of sensitization to topical polypeptides in BALB/c mice, a phenomenon associated with Th2 dominant immune response ( Lin et al , 2012 ). Whereas past work has focused on the effector functions of IL-9 in allergic inflammation and the role of IL-9 in contact dermatitis to polypeptides, our study of CHS in IL-9 −/− mice addresses its role in the sensitization/elicitation phases of this allergic reaction.…”

Section: Discussionmentioning

confidence: 99%

“…Blocking IL-9 inhibits airway remodeling and mastocytosis in a model of chronic lung inflammation ( Kearley et al , 2011 ). A recent study shows that Th9 cells are generated in vivo after epicutaneous sensitization by patch application with ovalbumin in mice ( Lin et al , 2012 ). PU.1, an ETS-family transcription factor, has since been identified as a main regulator of IL-9 production in human Th9 cells.…”

Section: Introductionmentioning

confidence: 99%

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IL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis

Liu

Harberts

Tammaro

et al. 2014

Journal of Investigative Dermatology

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The cytokine IL-9, derived primarily from T-helper (Th)-9 lymphocytes, promotes expansion of the Th2 subset and is implicated in the mechanisms of allergic asthma. We hypothesize that IL-9 also plays a role in human allergic contact dermatitis (ACD). To investigate this hypothesis, skin biopsy specimens of positive patch test sites from non-atopic patients were assayed using qPCR and immunohistochemistry. Along with Th2 associated cytokines, IFN-γ, IL-4, and IL-17A, expression of IL-9, and PU.1, a Th9-associated transcription factor, were elevated when compared to paired normal skin. Immunohistochemistry on ACD skin biopsies identified PU.1+CD3+, and PU.1+CD4+ cells, consistent with Th9 lymphocytes, in the inflammatory infiltrate. PBMC from nickel-allergic patients, but not non-allergic controls, show significant IL-9 production in response to nickel. Blocking studies with monoclonal antibodies to HLA-DR (but not HLA-A, B, C) or chloroquine significantly reduced this nickel-specific IL-9 production. Additionally, blockade of IL-9 or IL-4 enhanced allergen-specific IFN-γ production. A contact hypersensitivity model using IL-9−/− mice, shows enhanced Th1 lymphocyte immune responses, when compared to WT mice, consistent with our human in vitro data. This study demonstrates that IL-9, through its direct effects on Th1 and ability to promote IL-4 secretion, has a regulatory role for Th1 lymphocytes in ACD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis

Liu

Harberts

Tammaro

et al. 2014

Journal of Investigative Dermatology

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“…However, truly epicutaneous sensitization models to relevant allergens are not well established so far. They often rely on artificial barrier disruption, and in most studies the food allergen ovalbumin has been used (Wang et al , 2009; Lin et al , 2012; Matsumoto and Saito, 2013; Savinko et al , 2013). We recently succeeded establishing a percutaneous sensitization protocol for Der p 1 (Szalai et al , 2012).…”

Section: Introductionmentioning

confidence: 99%

Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation

Stremnitzer

Manzano-Szalai

Willensdorfer

et al. 2015

Journal of Investigative Dermatology

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Papain is commonly used in food, pharmaceutical, textile, and cosmetic industries and is known to induce occupational allergic asthma. We have previously shown that the papain-like cysteine protease Dermatophagoides pteronyssinus 1 from house dust mite exhibits percutaneous sensitization potential. We aimed here to investigate the potential of papain itself in epicutaneous sensitization. The effects of papain on tight junction (TJ) proteins were tested in vitro in human primary keratinocytes. Using C57BL/6 wild-type and Toll-like receptor 4 (TLR4)-deficient mice, we analyzed the sensitization potential of papain, its effects on the skin barrier, and immune cell recruitment. Our results show that papain affects the skin barrier by increasing transepidermal water loss, degrading TJ proteins and inducing vasodilation. When topically applied, papain exhibited a high epicutaneous inflammatory potential by recruiting neutrophils, mast cells, and CD3-positive cells and by induction of a TH2-biased antibody response. However, its high potency for specific sensitization via the skin was TLR4 independent and, in spite of its capacity to degrade epidermal TJ proteins, does not rely on its enzymatic function. From our data, we conclude that papain has all features to act as a strong allergen via the skin.

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“…Epicutaneous exposure to ovalbumin (OVA)/SEB has been shown to induce elevated antigen-specific serum IgE levels [8] and dermal infiltration of eosinophils, mast cells, and T cells with a mixed Th1/Th2 cytokine and chemokine expression profile. Epicutaneous sensitization with OVA also induces a Th17 and Th9 response [9,10]. …”

Section: Introductionmentioning

confidence: 99%

A legume product fermented by Saccharomyces cerevisiae modulates cutaneous atopic dermatitis-like inflammation in mice

Yeh

Jung

Huang

et al. 2014

BMC Complement Altern Med

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BackgroundIsoflavone-containing soy products modulate allergic inflammation in mice. In our previously study, IFN-γ and IL-10 production increased in mice fed with Saccharomyces cerevisiae legume fermented product (SCLFP), demonstrating that SCLFP had immunomodulatory activity. In this study, we tested the anti-inflammatory effects of SCLFP in a mouse model of cutaneous atopic dermatitis inflammation induced by epicutaneous sensitization.MethodsEpicutaneous exposure to protein allergens plus Staphylococcal enterotoxin B induced a T helper (Th)-2–dominant immune response as well as cutaneous atopic dermatitis-like inflammation in BALB/c mice. The thickness of the skin epithelium, eosinophil migration, and T helper responses were determined in patched skin and draining lymph nodes of mice fed with and without SCLFP.ResultsEpicutaneous exposure to protein allergens plus Staphylococcal enterotoxin B induced a T helper (Th)-2–dominant immune response as well as cutaneous atopic dermatitis-like inflammation in BALB/c mice. SCLFP feeding attenuated this cutaneous Th2 response, as evidenced by decreased thickening of the epidermis, less eosinophil infiltration, and lower levels of IL-5, IL-13, and CXCL11 expression compared to controls. Oral administration of SCLFP also modulated Th1 responses in draining lymph nodes, with lower levels of IFN-γ, IL-4, and IL-17 expression.ConclusionOral intake of SCLFP modulated the induced Th2 inflammatory responses in skin and might have potential applications for the prevention and treatment of atopic dermatitis.

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Epicutaneous Sensitization with Protein Antigen Induces Th9 Cells

Cited by 9 publications

References 10 publications

IL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis

IL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis

Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation

A legume product fermented by Saccharomyces cerevisiae modulates cutaneous atopic dermatitis-like inflammation in mice

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