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Studies examining the role of IL-33 and IL1RL1 (ST2) in human ILC2 function

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posted on 2022-11-30, 11:03 authored by Mohammed Alshammari

Asthma is a heterogeneous disease characterised by frequent airway obstruction in the lung resulting from allergic (atopic) or non-allergic (non-atopic) triggers. Allergic asthma is associated with airway inflammation and is characterised by the infiltration of inflammatory cells including eosinophils, mast cells and T-helper 2 cells (TH2). Several soluble mediators have been shown to play a critical role in the pathogenicity of allergic asthma. These mediators include the hallmark TH2 cytokines interleukin (IL)-4, IL-5 and IL-13 and the epithelial-derived cytokines IL-25, IL-33 and Thymic Stromal Lymphopoietin (TSLP). Until recently, it was believed that allergic inflammation is linked to the CD4+ TH2 cells and mast cells. However, the recently discovered group 2 innate lymphoid cells (ILC2s) have been found to play an important role in mucosal surfaces including airway tracts, as they have the capacity to produce TH2 cytokines including IL-4, IL-5 and IL-13 upon stimulation with IL-25, IL-33 and TSLP. Interleukin 1 receptor-like 1 (IL1RL1), also known as ST2, with its ligand IL33, induces allergic inflammation due to the release of type 2 cytokines. The biology of ST2 is complex because it is expressed in two forms, the soluble protein sST2, which down regulates TH2 responses, and the transmembrane form ST2 (ST2 or ST2L). Several studies have demonstrated that ST2 is expressed by ILC2s in mice; however, it is unclear from the literature whether human ILC2s express ST2. Therefore, the aims of this project were to validate antibodies to ST2 and to use validated antibodies to examine ST2 expression on human peripheral blood samples, in particular ILC2s. We hypothesised that ST2 may be upregulated on human ILC2s from asthmatic subjects compared to healthy controls. The results demonstrated that most of the commonly used ST2 antibodies were not specific to ST2, calling into question several of the published reports in the literature. Despite identifying an appropriate antibody for use in flow cytometry, it was not possible to complete the assessment of ST2 expression in asthma due to the COVID19 pandemic.

History

Supervisor(s)

David Cousins; Yassine Amrani

Date of award

2022-10-21

Author affiliation

Department of Infection, Immunity & Inflammation

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD

Language

en

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