Supplementary MaterialsS1 Desk: Person data depicted in Fig 1A. S9 Desk:

Supplementary MaterialsS1 Desk: Person data depicted in Fig 1A. S9 Desk: Person data depicted in Fig 4A. (XLSX) pone.0134226.s009.xlsx (51K) GUID:?61A40037-A240-4D49-B782-B9F80A381671 S10 Desk: Person data depicted in Fig 4B. (XLSX) pone.0134226.s010.xlsx (52K) GUID:?B624D6FE-EEA6-4E66-8B16-2954B60F2811 S11 Desk: Specific data depicted in Fig 5A. (XLSX) pone.0134226.s011.xlsx Limonin manufacturer (61K) GUID:?713AAB74-FA72-4095-9849-0A3F016B753F S12 Desk: Specific data depicted in Fig 5B. (XLSX) pone.0134226.s012.xlsx (59K) GUID:?DC2C118B-33F9-4638-B83E-95057976CAAE S13 Desk: Specific data depicted in Fig 6A. (XLSX) pone.0134226.s013.xlsx (43K) GUID:?C09FA5D1-DC9D-4875-AE88-6AA25064FA55 S14 Table: Individual data depicted in Fig 6B. (XLSX) pone.0134226.s014.xlsx (44K) GUID:?2F58D216-FC75-44AC-9643-E00B4A3414C3 S15 Table: Individual data depicted in Fig 6C. (XLSX) pone.0134226.s015.xlsx (43K) GUID:?82B091B2-8B33-4B29-ABD4-EBFB8ED4F4C8 S16 Table: Individual data depicted in Fig 6D. (XLSX) pone.0134226.s016.xlsx (43K) GUID:?8367426D-5196-4920-B684-E38FDB339E76 Data Availability StatementAll relevant data are available in the manuscript and its Supporting Information files. Abstract Background IL-25, IL-33 and TSLP are produced predominantly by epithelial cells and are known to induce Th2-type cytokines. Th2-type cytokines are involved not only in host defense Limonin manufacturer against nematodes, but also NF-ATC in the development of Th2-type allergic diseases. TSLP was reported to be crucial for development of allergic airway inflammation in mice after inhalation of allergens to which they had been sensitized epicutaneously (EC) beforehand. However, the functions of IL-25 and IL-33 in the setting remain unclear. Methods Mice deficient in IL-25 and IL-33 were sensitized EC with ovalbumin (OVA) and then challenged intranasally with OVA. Airway inflammation, the number of inflammatory cells in bronchoalveolar lavage fluids (BALFs) and airway hyperresponsiveness (AHR) in the mice were decided, respectively, by histological analysis, with a hemocytometer, and by using plethysmograph chambers with a ventilator. Expression of mRNA in the skin and lungs was determined by quantitative PCR, while the BALF levels of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) and the serum levels of IgE were determined by ELISA. Results Normal OVA-specific Limonin manufacturer Th2- and Th17-cell responses of lymph nodes and spleens were observed in IL-25-deficient (IL-25-/-) and IL-33-/- mice after EC sensitization with OVA. Nevertheless, the number of eosinophils, but not neutrophils, in the BALFs, and the levels of Th2 cytokines, but not Th17 cytokines, in the lungs were significantly decreased in the IL-25-/- and IL-33-/- mice pre-sensitized EC with OVA, followed by inhalation of OVA, whereas their levels of AHR and OVA-specific serum IgE were normal. Conclusions Both IL-25 and IL-33 are critical for induction of Th2-type cytokine-mediated allergic airway eosinophilia, but not Th17-type cytokine-mediated airway neutrophilia, at the local sites of lungs in the challenge phase of mice sensitized EC with OVA. They do not affect OVA-specific T-cell induction in the sensitization phase. Introduction Sensitization Limonin manufacturer with allergens via the upper and lower respiratory tracts due to dysfunction and/or disruption of epithelial barriers is considered to be a major route of development of asthma [1]. Transdermal allergen sensitization due to dysfunction and/or disruption of epidermal barriers is recently recognized to be another route [2C4]. In support of this, in spite of the fact that filaggrin, which is known to be crucial for formation of epidermal barriers, is expressed in the skin but not in the lung, genetic deficiency of resulted in increased susceptibility to asthma as well as peanut allergy [5]. Thus, filaggrin mutations may be a predisposing factor for such diseases [5]. However, the molecular mechanisms of the transdermal allergen sensitization pathway are not fully comprehended. IL-25 (an IL-17 cytokine family member), IL-33 (an IL-1 cytokine family member) and thymic stromal lymphopoietin (TSLP; an IL-7 cytokine family member) are produced predominantly by epithelial cells such as airway epithelial cells and keratinocytes. These cytokines can induce production of Th2-type cytokines such Limonin manufacturer as IL-4, IL-5 and/or IL-13 by various types of cells, including Th2 cells, NKT cells, mast cells, basophils, eosinophils and type 2 innate lymphoid cells (ILC2) [6C8]. IL-25, IL-33 and/or TSLP were increased in specimens from patients with asthma [9C11] and in inflamed skin lesions of patients with atopic dermatitis [12C15]. Therefore, these cytokines may be produced by epithelial cells after exposure to allergens, contributing to the development of allergic diseases by inducing early immune responses leading to sensitization to allergens. That is, keratinocyte-derived IL-25, IL-33 and/or TSLP may be involved in sensitization to allergens, contributing.