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

1
Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, Taipei 23561, Taiwan
2
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
3
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan
4
Department of Clinical Pathology, Far Eastern Memorial Hospital, New Taipei City 22060, Taiwan
5
School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei 11031, Taiwan
6
Ph.D. Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
7
Department of Biotechnology, National Formosa University, Yunlin County 63201, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(4), 1231; https://doi.org/10.3390/ijms19041231
Received: 29 March 2018 / Revised: 12 April 2018 / Accepted: 14 April 2018 / Published: 18 April 2018
(This article belongs to the Special Issue Molecular Research on Mucosal Immunity)
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. View Full-Text
Keywords: IL-7Rα; pediatric asthma; thymic stromal lymphopoietin; thymic stromal lymphopoietin receptor IL-7Rα; pediatric asthma; thymic stromal lymphopoietin; thymic stromal lymphopoietin receptor
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Lin, S.-C.; Cheng, F.-Y.; Liu, J.-J.; Ye, Y.-L. Expression and Regulation of Thymic Stromal Lymphopoietin and Thymic Stromal Lymphopoietin Receptor Heterocomplex in the Innate–Adaptive Immunity of Pediatric Asthma. Int. J. Mol. Sci. 2018, 19, 1231.

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