scholarly journals Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 688
Author(s):  
Jeng-Chang Chen ◽  
Cheng-Chi Chan ◽  
Nai-Chun Ting ◽  
Ming-Ling Kuo
Keyword(s):  
Periodic Acid ◽  
Later Life ◽  
Specific Ige ◽  
Allergen Exposure ◽  
Th2 Cells ◽  
Gene Expressions ◽  
Periodic Acid Schiff ◽  
T Helper 2 ◽  
Th2 Cytokine ◽  
Th2 Cell

We previously demonstrated that fetal allergen exposure caused T-helper 2 (Th2) cell sensitization. Although neonates are immunologically more mature than fetuses, asthmatic lungs were reportedly mitigated by neonatal allergen administration, mechanically referring to regulatory T-cells and TGF-β signaling but lacking the immunological profiles after neonatal exposure. To reappraise the immunological outcome of neonatal allergen exposure, we injected adjuvant-free ovalbumin intraperitoneally into 2-day-old BALB/c neonates, followed by aerosolized ovalbumin inhalation in adulthood. Mice were examined for the immunological profiles specifically after neonatal exposures, lung function and histology (hematoxylin-eosin or periodic acid Schiff staining), and gene expressions of intrapulmonary cytokines (IL-4, IL-5, IL-13 and IFN-γ) and chemokines (CCL17, CCL22, CCL11 and CCL24). Neonatal ovalbumin exposure triggered Th2-skewed sensitization and ovalbumin-specific IgE production. Subsequent ovalbumin inhalation in adulthood boosted Th2 immunity and caused asthmatic lungs with structural and functional alterations of airways. Gender difference mainly involved airway hyperresponsiveness and resistance with greater female susceptibility to methacholine bronchospastic stimulation. In lungs, heightened chemoattractant gene expressions were only granted to neonatally ovalbumin-sensitized mice with aerosolized ovalbumin stress in adulthood, and paralleled by upregulated Th2 cytokine genes. Thus, aeroallergen stress in atopic individuals might upregulate the expression of intrapulmonary chemoattractants to recruit Th2 cells and eosinophils into the lungs, pathogenically linked to asthma development. Conclusively, murine neonates were sensitive to allergen exposures. Exposure events during neonatal stages were crucial to asthma predisposition in later life. These findings from a murine model point to allergen avoidance in neonatal life, possibly even very early in utero, as the best prospect of primary asthma prevention.

scholarly journals T-cell–intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy

2016 ◽  
Vol 113 (5) ◽  
pp. E568-E576 ◽  
Author(s):  
Jimena Perez-Lloret ◽  
Isobel S. Okoye ◽  
Riccardo Guidi ◽  
Yashaswini Kannan ◽  
Stephanie M. Coomes ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Allergic Diseases ◽  
Treg Cells ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Cytokines And Chemokines ◽  
Th2 Cell

There is a paucity of new therapeutic targets to control allergic reactions and forestall the rising trend of allergic diseases. Although a variety of immune cells contribute to allergy, cytokine-secreting αβ+CD4+ T-helper 2 (TH2) cells orchestrate the type-2–driven immune response in a large proportion of atopic asthmatics. To identify previously unidentified putative targets in pathogenic TH2 cells, we performed in silico analyses of recently published transcriptional data from a wide variety of pathogenic TH cells [Okoye IS, et al. (2014) Proc Natl Acad Sci USA 111(30):E3081–E3090] and identified that transcription intermediary factor 1 regulator-alpha (Tif1α)/tripartite motif-containing 24 (Trim24) was predicted to be active in house dust mite (HDM)- and helminth-elicited Il4gfp+αβ+CD4+ TH2 cells but not in TH1, TH17, or Treg cells. Testing this prediction, we restricted Trim24 deficiency to T cells by using a mixed bone marrow chimera system and found that T-cell–intrinsic Trim24 is essential for HDM-mediated airway allergy and antihelminth immunity. Mechanistically, HDM-elicited Trim24−/− T cells have reduced expression of many TH2 cytokines and chemokines and were predicted to have compromised IL-1–regulated signaling. Following this prediction, we found that Trim24−/− T cells have reduced IL-1 receptor (IL-1R) expression, are refractory to IL-1β–mediated activation in vitro and in vivo, and fail to respond to IL-1β–exacerbated airway allergy. Collectively, these data identify a previously unappreciated Trim24-dependent requirement for IL-1R expression on TH2 cells and an important nonredundant role for T-cell–intrinsic Trim24 in TH2-mediated allergy and antihelminth immunity.

Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4565-4573 ◽  
Author(s):  
Akira Suto ◽  
Hiroshi Nakajima ◽  
Koichi Hirose ◽  
Kotaro Suzuki ◽  
Shin-ichiro Kagami ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
Germ Line ◽  
Allergic Diseases ◽  
Specific Ige ◽  
T Helper 2 ◽  
Th2 Cell ◽  
Interleukin 21

Interleukin 21 (IL-21) has recently been identified as a multifunctional cytokine that induces the proliferation of T cells and B cells and differentiation of natural killer cells. To determine whether IL-21 regulates IL-4–mediated immune responses, we examined the effect of IL-21 on antigen-specific IgE production in mice. We also examined the effect of IL-21 on IL-4–induced IgE production from B cells and antigen-induced T-helper 2 (Th2) cell differentiation. The in vivo injection of IL-21 prevented antigen-specific IgE but not IgG2a production on immunization. IL-21 did not affect Th2 cell differentiation or IL-4 production from CD4+ T cells but directly inhibited IL-4–induced IgE production from B cells at single-cell levels. Moreover, IL-21 inhibited IL-4–induced germ line Cε transcription in B cells without the inhibition of signal transducer and activator of transcription 6 (Stat6) activation. Taken together, these results indicate that IL-21 down-regulates IgE production from IL-4–stimulated B cells through the inhibition of germ line Cε transcription and thus suggest that IL-21 may be useful for the treatment of IgE-dependent allergic diseases.

Hodgkin/Reed-Sternberg Cells Induce Fibroblasts to Secrete Eotaxin, a Potent Chemoattractant for T Cells and Eosinophils

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2065-2071 ◽  
Author(s):  
Franziska Jundt ◽  
Ioannis Anagnostopoulos ◽  
Kurt Bommert ◽  
Florian Emmerich ◽  
Gerd Müller ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Neutralizing Antibodies ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Allergic Inflammation ◽  
Dermal Fibroblasts ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Th2 Cell ◽  
Necrosis Factor

Hodgkin’s disease is histopathologically characterized by the relative scarcity of neoplastic Hodgkin and Reed-Sternberg cells and for yet unknown reasons by an abundant reactive background of T lymphocytes and often eosinophils. Eotaxin is a CC-chemokine attracting eosinophils and T helper 2 (Th2) cells in allergic inflammation. We now report that eotaxin is strongly expressed in fibroblasts of Hodgkin’s disease tissues, whereas Hodgkin/Reed-Sternberg cells do not express this chemokine. In tissue culture, Hodgkin’s disease tumor cells induce eotaxin expression in cocultured dermal fibroblasts in a concentration leading to a specific chemotactic response of a Th2 cell clone. Production of tumor necrosis factor- (TNF-) by Hodgkin/Reed-Sternberg cells appears to be responsible for this induction, because blocking of TNF- by neutralizing antibodies prevented fibroblast eotaxin expression. Our data suggest that eotaxin is involved in the pathobiology of Hodgkin’s disease by contributing to eosinophil and T-lymphocyte recruitment.

SOCS proteins in T helper cell differentiation: implications for allergic disorders?

2004 ◽  
Vol 6 (22) ◽  
pp. 1-11 ◽  
Author(s):  
Hiromasa Inoue ◽  
Masato Kubo
Keyword(s):  
Cell Differentiation ◽  
Specific Ige ◽  
Th2 Cells ◽  
T Helper ◽  
T Helper 2 ◽  
Th Cell ◽  
Socs Proteins ◽  
Th2 Differentiation ◽  
Allergic Disorders

Asthma, allergic rhinitis and atopic dermatitis are allergic immune disorders characterised by a predominance of T helper 2 (Th2) cells, the resulting elevation of allergen-specific IgE, and mast-cell- and basophil-associated inflammation. The cytokine environment at the site of the initial antigen stimulation determines the direction of Th-cell differentiation into Th1 or Th2 cells. The SOCS (suppressor of cytokine signalling) proteins are implicated in the control of the balance between Th1 and Th2 cells in this process. SOCS3 is predominantly expressed in Th2 cells and inhibits Th1 differentiation; conversely, SOCS5 is expressed predominantly in Th1 cells and inhibits Th2 differentiation. Here, we discuss the role of SOCS proteins in Th-cell differentiation and explore the potential of SOCS proteins as targets for therapeutic strategies in allergic disorders.

The presence of LPS in OVA inhalations affects airway inflammation and AHR but not remodeling in a rodent model of asthma

2012 ◽  
Vol 303 (1) ◽  
pp. L54-L63 ◽  
Author(s):  
Kimitake Tsuchiya ◽  
Sana Siddiqui ◽  
Paul-André Risse ◽  
Nobuaki Hirota ◽  
James G. Martin
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Airway Remodeling ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Brown Norway ◽  
Cell Hyperplasia ◽  
Periodic Acid Schiff ◽  
Th2 Cytokine ◽  
Ifn Γ

Ovalbumin (OVA) is the most frequently used allergen in animal models of asthma. Lipopolysaccharide (LPS) contaminating commercial OVA may modulate the evoked airway inflammatory response to OVA. However, the effect of LPS in OVA on airway remodeling, especially airway smooth muscle (ASM) has not been evaluated. We hypothesized that LPS in commercial OVA may enhance allergen-induced airway inflammation and remodeling. Brown Norway rats were sensitized with OVA on day 0. PBS, OVA, or endotoxin-free OVA (Ef-OVA) was instilled intratracheally on days 14, 19, 24. Bronchoalveolar lavage (BAL) fluid, lung, and intrathoracic lymph node tissues were collected 48 h after the last challenge. Immunohistochemistry for α-smooth muscle actin, Periodic-Acid-Schiff staining, and real-time qPCR were performed. Airway hyperresponsiveness (AHR) was also measured. BAL fluid macrophages, eosinophils, neutrophils, and lymphocytes were increased in OVA-challenged animals, and macrophages and neutrophils were significantly lower in Ef-OVA-challenged animals. The ASM area in larger airways was significantly increased in both OVA and Ef-OVA compared with PBS-challenged animals. The mRNA expression of IFN-γ and IL-13 in lung tissues and IL-4 in lymph nodes was significantly increased by both OVA and Ef-OVA compared with PBS and were not significantly different between OVA and Ef-OVA. Monocyte chemoattractant protein (MCP)-1 in BAL fluid and AHR were significantly increased in OVA but not in Ef-OVA. LPS contamination in OVA contributes to the influx of macrophages and MCP-1 increase in the airways and to AHR after OVA challenges but does not affect OVA-induced Th1 and Th2 cytokine expression, goblet cell hyperplasia, and ASM remodeling.

scholarly journals OK-432 Acts as Adjuvant to Modulate T Helper 2 Inflammatory Responses in a Murine Model of Asthma

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Cheng-Jang Wu ◽  
Pin-Hsun Tseng ◽  
Cheng-Chi Chan ◽  
Sara Quon ◽  
Li-Chen Chen ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Allergic Diseases ◽  
Adjuvant Effect ◽  
T Helper 2 ◽  
Th2 Cytokine ◽  
Th2 Cell ◽  
Prophylactic Vaccination ◽  
Streptococcal Preparation ◽  
Th1 Polarization

Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an appropriate adjuvant can elicit suitable systemic immunity to protect individuals from disease. Although much has been learned about Th1-favored immunomodulation of OK-432, a streptococcal preparation with antineoplastic activity, little is known about its adjuvant effect for allergic diseases. Herein, we demonstrate that OK-432 acts as an adjuvant to favor a systemic Th1 polarization with an elevation in interferon- (IFN-) γ and ovalbumin- (OVA-) immunoglobulin (Ig) G2a. Prior vaccination with OK-432 formulated against OVA attenuated lung eosinophilic inflammation and Th2 cytokine responses that were caused by challenging with OVA through the airway. This vaccination with OK-432 augmented the ratios of IFN-γ/interleukin- (IL-) 4 cytokine and IgG2a/IgG1 antibody compared to the formulation with Th2 adjuvant aluminum hydroxide (Alum) or antigen only. The results obtained in this study lead us to propose a potential novel adjuvant for clinical use such as prophylactic vaccination for pathogens and immunotherapy in atopic diseases.

Hodgkin/Reed-Sternberg Cells Induce Fibroblasts to Secrete Eotaxin, a Potent Chemoattractant for T Cells and Eosinophils

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2065-2071 ◽  
Author(s):  
Franziska Jundt ◽  
Ioannis Anagnostopoulos ◽  
Kurt Bommert ◽  
Florian Emmerich ◽  
Gerd Müller ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Neutralizing Antibodies ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Allergic Inflammation ◽  
Dermal Fibroblasts ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Th2 Cell ◽  
Necrosis Factor

Abstract Hodgkin’s disease is histopathologically characterized by the relative scarcity of neoplastic Hodgkin and Reed-Sternberg cells and for yet unknown reasons by an abundant reactive background of T lymphocytes and often eosinophils. Eotaxin is a CC-chemokine attracting eosinophils and T helper 2 (Th2) cells in allergic inflammation. We now report that eotaxin is strongly expressed in fibroblasts of Hodgkin’s disease tissues, whereas Hodgkin/Reed-Sternberg cells do not express this chemokine. In tissue culture, Hodgkin’s disease tumor cells induce eotaxin expression in cocultured dermal fibroblasts in a concentration leading to a specific chemotactic response of a Th2 cell clone. Production of tumor necrosis factor- (TNF-) by Hodgkin/Reed-Sternberg cells appears to be responsible for this induction, because blocking of TNF- by neutralizing antibodies prevented fibroblast eotaxin expression. Our data suggest that eotaxin is involved in the pathobiology of Hodgkin’s disease by contributing to eosinophil and T-lymphocyte recruitment.

Mast cells produce interleukin-25 upon FcεRI-mediated activation

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3594-3596 ◽  
Author(s):  
Kei Ikeda ◽  
Hiroshi Nakajima ◽  
Kotaro Suzuki ◽  
Shin-ichiro Kagami ◽  
Koichi Hirose ◽  
...  
Keyword(s):  
Mast Cells ◽  
Immunoglobulin E ◽  
Th2 Cells ◽  
Cross Linking ◽  
Dependent Manner ◽  
T Helper ◽  
T Helper 2 ◽  
Protein Levels ◽  
Th2 Cell ◽  
Interleukin 25

Interleukin-25 (IL-25) is a recently described T helper 2 (TH2) cell–derived cytokine that belongs to the IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non–T-cell population. Here, we show that mast cells are also potent IL-25–producing cells. When bone marrow–derived mast cells were stimulated by immunoglobulin E cross-linking, IL-25 mRNA was induced within 30 minutes in a calcineurin-dependent manner, and the levels of IL-25 mRNA were comparable with those of activated TH2 cells. Production of IL-25 by mast cells was also detected at protein levels by immunoblotting. These results suggest that mast cells may enhance TH2-type immune response by producing IL-25.

scholarly journals Th2 cytokines-DUOX2-ROS-HMGB1 translocation axis is important in the pathogenesis of allergic rhinitis

2021 ◽  
Vol 135 (3) ◽  
pp. 483-494
Author(s):  
Hyun Jin Min ◽  
Joon Soon Park ◽  
Kyung Soo Kim ◽  
Seung Yong Park ◽  
Honghwan Choi ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Murine Model ◽  
Immunoglobulin E ◽  
Periodic Acid ◽  
High Mobility ◽  
Upper Airway ◽  
Th2 Cytokines ◽  
Periodic Acid Schiff ◽  
Th2 Cytokine

Abstract The function of high-mobility group box 1 (HMGB1) varies according to its location. However, the translocation mechanism behind HMGB1 remains unclear. We hypothesize that type 2 helper T cell (Th2) cytokines are involved in the translocation of HMGB1 in the upper airway epithelium. We investigated the mechanism behind HMGB1 translocation using Th2 cytokine stimulation and examined the clinical significance of HMGB1 translocation in allergic rhinitis (AR). Cytoplasmic and extracellular HMGB1 were increased in AR. Inhibiting HMGB1 translocation with glycyrrhizic acid (GA) decreased the level of antigen-specific immunoglobulin E (IgE), the degree of Periodic Acid–Schiff (PAS), and Sirius Red staining in the murine model. The in vivo reactive oxygen species (ROS) level in the nasal mucosa was higher in the mice with AR than in the controls. Th2 cytokine-induced up-regulation of the ROS and translocation of HMGB1 by Th2 cytokines was dependent on the generated ROS. The ROS level also increased in the murine model. We suggest that the Th2 cytokine-dual oxidase (DUOX)2-ROS-HMGB1 translocation axis is important in AR pathogenesis.

scholarly journals The Other T Helper Cells in Asthma Pathogenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Christina Vock ◽  
Hans-Peter Hauber ◽  
Michael Wegmann
Keyword(s):  
T Helper Cells ◽  
Airway Remodeling ◽  
Th2 Cells ◽  
Variable Degree ◽  
T Helper ◽  
Mucus Production ◽  
T Helper 2 ◽  
Cell Functions ◽  
Helper Cells ◽  
Th2 Cell

The complex phenotype of allergic bronchial asthma involves a variable degree of bronchoobstruction, increased mucus production, and airway remodeling. So far it is suggested that it arises from multiple interactions of infiltrating and structural cells in the context of chronic airway inflammation that is orchestrated by T helper 2 (TH2) cells. By secreting a plethora of typical mediators such as interleukin (IL) 4, IL-5, and IL-13, these cells hold a key position in asthma pathogenesis. However, therapeutic approaches targeting these TH2-type mediators failed to improve asthma symptoms and impressively showed that asthma pathogenesis cannot be reduced by TH2 cell functions. Recently, other T helper cells, that is, TH9 and TH17 cells, have been identified and these cells also contribute to asthma pathogenesis, the processes leading to formation or aggravation of asthma. Furthermore, TH25 cells, TH3 cells, and regulatory T cells have also been implicated in asthma pathogenesis. This paper aims at summarizing recent insights about these new T helper cells in asthma pathogenesis.

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