Expression and Regulation of Thymic Stromal Lymphopoietin and Thymic Stromal Lymphopoietin Receptor Heterocomplex in the Innate–Adaptive Immunity of Pediatric Asthma

Abstract

Asthma is a chronic inflammatory disease affecting the airway, and it is characterized by a wheezing breathing sound, variable airflow obstruction and the presence of inflammatory cells in the submucosa of the bronchi. Viral infection, pollutants and sensitivity to aeroallergens damage the epithelium from childhood, which causes asthma. The pathogenesis of asthma includes pathways of innate stimulation by environmental microbes and irritant pathogens. Damaged epithelial cells produce thymic stromal lymphopoietin (TSLP) and stimulate myeloid dendritic cell maturation through the thymic stromal lymphopoietin receptor (TSLPR) heterocomplex. TSLP-activated myeloid dendritic cells promote naive CD4+ T cells to differentiate into T helper type 2 (Th2) phenotype CD4+ T cells. Re-exposure to allergens or environmental stimuli causes an adaptive immune response. TSLP-activated dendritic cells expressing the OX40 ligand (OX40L; CD252) trigger naive CD4+ T cells to differentiate into inflammatory Th2 effector cells secreting the cytokines interleukin-4, 5, 9, and 13 (IL-4, IL-5, IL-9 and IL-13), and the dendritic cells (DCs) promote the proliferation of allergen-specific Th2 memory cells. Allergen presentation by Th2 cells through its interaction with their receptors in the presence of major histocompatibility complex (MHC) class II on B cells and through costimulation involving CD40 and CD40L interactions results in immunoglobulin class switching from IgM to IgE. DCs and other blood cell subsets express the TSLPR heterocomplex. The regulatory mechanism of the TSLPR heterocomplex on these different cell subsets remains unclear. The TSLPR heterocomplex is composed of the IL-7Rα chain and TSLPR chain. Moreover, two isoforms of TSLP, short isoform TSLP (sfTSLP) and long isoform TSLP (lfTSLP), have roles in atopic and allergic development. Identifying and clarifying the regulation of TSLPR and IL-7Rα in pediatric asthma are still difficult, because the type of blood cell and the expression for each blood cell in different stages of atopic diseases are poorly understood. We believe that further integrated assessments of the regulation mechanism of the TSLP–TSLPR heterocomplex axis in vitro and in vivo can provide a faster and earlier diagnosis of pediatric asthma and promote the development of more effective preventive strategies at the onset of allergies.

E3 Ubiquitin Ligase March1 Facilitates OX40L Expression in Allergen-Stimulated Dendritic Cells Through Mediating the Ubiquitination of HDAC11

“…The DCs expressing OX40L are an inducer of Th2 differentiation in asthma. 30 , 31 OX40L affects the regulation of DCs to Th2 cells differentiation in asthma. Hence, we thought that exploring the expression mechanism of OX40L in DCs is very meaningful for understanding the pathogenesis of asthma.…”

Cytokines Activating ILCs2 in Patients With Obesity Before and After Bariatric Surgery Shortened Title: ILCs2 in Patients With Obesity

“…It was found that the serum levels of TSLP may be suitable as a biomarker for prediction of prognosis in a subgroup of patients with sepsis who are exhibiting hyperleukocytosis and a high neutrophil ratio [20]. Moreover its role was con rmed in atopic diseases [21], pediatric allergic asthma [22] and atopic dermatitis [23] where may be even a potential therapeutic agent. Much less is known about its role in obesity.…”

Advanced Molecular Knowledge of Therapeutic Drugs and Natural Products Focusing on Inflammatory Cytokines in Asthma

“…IL-25 is released when the cell is exposed to protease-containing antigens, such as house dust mite, and it is released by immune cells such as Th2 cells, mast cells, basophiles, and eosinophils [23,24]. TSLP is a four-helix bundle cytokine that can activate DCs, NKT cells, mast cells, and eosinophils to interact with cytokines and inflammatory mediators on the airway smooth muscle of patients with asthma [25]. In an asthma model, TSLP can upregulate natural killer T cells to increase IL-13 production and decrease airway hyperreactivity [26].…”

“…TSLP-like IL-33 and IL-25 can also stimulate ILC2 to increase the production of Th2-type cytokines [16]. In patients with asthma, re-exposure to allergens (such as dust mites, animal dander, dust, mold spores, and pollen) or environmental stimuli can cause an adaptive immune response [25]. Environmental antigens are immune-regulated, and are recognized by DCs, macrophages, B lymphocytes, and several other cell types that belonged to antigen presenting cells (APCs) [17].…”

“…TSLP, IL-25, and IL-33 can directly stimulate ILC2 to secrete Th2 cytokines, and they induce antigen-specific IL-5 CD4+ T cells and promote allergen-induced inflammation independent of IL-4 [40]. TSLP may play a fundamental role in the innate–adaptive interface in the pathology of asthma [25].…”