Eosinophilic inflammation of chronic rhinosinusitis with nasal polyps is related to OX40 ligand expression

Boita, Monica; Garzaro, Massimiliano; Raimondo, Luca; Riva, Giuseppe; Mazibrada, Jasenka; Pecorari, Giancarlo; Bucca, Caterina; Bellone, Graziella; Vizio, Barbara; Heffler, Enrico; Ricciardolo, Fabio Luigi Massimo; Rolla, Giovanni

doi:10.1177/1753425914523460

Cited by 18 publications

(13 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, several groups reported that TSLP mRNA was significantly elevated in eosinophilic NPs in the US, Canada, China, Japan and Italy. 7,67–71 Although it is notably difficult to detect TSLP protein in clinical samples by commercially available detection systems, Nagarkar et al and Allakhverdi et al found that TSLP activity was significantly elevated in NPs compared to control sinus tissue. 7,67 This indicates that TSLP protein is elevated in NPs.…”

Section: Type 2 Inflammation and Epithelial Cytokines In Eosinophilicmentioning

confidence: 99%

Immunopathology of chronic rhinosinusitis

Kato

2015

Allergology International

235

205

View full text Add to dashboard Cite

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and sinuses which persists for at least 12 weeks. CRS can be divided into two phenotypes dependent on the presence of nasal polyps (NPs); CRS with NPs (CRSwNP) and CRS without NPs (CRSsNP). Immunological patterns in the two diseases are known to be different. Inflammation in CRSsNP is rarely investigated and limited studies show that CRSsNP is characterized by type 1 inflammation. Inflammation in CRSwNP is well investigated and CRSwNP in Western countries shows type 2 inflammation and eosinophilia in NPs. In contrast, mixed inflammatory patterns are found in CRSwNP in Asia and the ratio of eosinophilic NPs and non-eosinophilic NPs is almost 50:50 in these countries. Inflammation in eosinophilic NPs is mainly controlled by type 2 cytokines, IL-5 and IL-13, which can be produced from several immune cells including Th2 cells, mast cells and group 2 innate lymphoid cells (ILC2s) that are all elevated in eosinophilic NPs. IL-5 strongly induces eosinophilia. IL-13 activates macrophages, B cells and epithelial cells to induce recruitment of eosinophils and Th2 cells, IgE mediated reactions and remodeling. Epithelial derived cytokines, TSLP, IL-33 and IL-1 can directly and indirectly control type 2 cytokine production from these cells in eosinophilic NPs. Recent clinical trials showed the beneficial effect on eosinophilic NPs and/or asthma by monoclonal antibodies against IL-5, IL-4Rα, IgE and TSLP suggesting that they can be therapeutic targets for eosinophilic CRSwNP.

show abstract

Section: Type 2 Inflammation and Epithelial Cytokines In Eosinophilicmentioning

confidence: 99%

Immunopathology of chronic rhinosinusitis

Kato

2015

Allergology International

235

205

View full text Add to dashboard Cite

show abstract

“…TSLP and TSLP receptor have been found highly expressed in sinus mucosa of patients with CRSwNP [8–11], and a recent work by Golebski et al [22] was able to demonstrate that the TLR3 agonist and viral analog poly(I:C) were able to induce higher TSLP mRNA and protein expression in the epithelium isolated from nasal polyposis patients compared to epithelium form healthy controls, while a few and contrasting observations have been reported on the presence of IL-25 in CRS. IL-25 mRNA has been reported to be significantly elevated in ethmoid sinuses of CRSwNP compared to controls and CRSsNP by Lam et al [23].…”

Section: Discussionmentioning

confidence: 99%

“…TSLP has been found highly expressed in sinus mucosa of patients with CRSwNP [8–11] and epithelial production of IL-25, IL-33, and TSLP has emerged as critical epithelial factors that can initiate and amplify airway inflammation [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps

Boita

Bucca

Riva

et al. 2016

Journal of Immunology Research

Self Cite

View full text Add to dashboard Cite

Background. T2 inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) may be influenced by epithelial cytokines release (TSLP, IL-25, and IL-33). We investigated the release of TSLP, IL-25, and IL-33 by epithelial CRSwNP cells compared to epithelial sinus mucosa cells of patients with chronic rhinosinusitis without nasal polyps (CRSsNP). Methods. IL-25, IL-33, and TSLP were measured by ELISA in the supernatant of cell cultures derived by CRSwNP (9 patients, 6 atopic) and CRSsNP (7 patients, 2 atopic) in baseline condition and following stimulation with Dermatophagoides pteronyssinus (DP), Aspergillus fumigatus (AF), and poly(I:C). Results. CRSwNP epithelial cells released increased levels of IL-25 (from 0.12 ± 0.06 pg/ml to 0.27 ± 0.1 pg/ml, p < 0.01) and TSLP (from 0.77 ± 0.5 pg/ml to 2.53 ± 1.17 pg/ml, p < 0.001) following poly(I:C) stimulation, while CRSsNP epithelial cells released increased levels of IL-25 and IL-33 following AF and DP stimulation, respectively (IL-25: from 0.18 ± 0.07 pg/ml to 0.51 ± 0.1 pg/ml, p < 0.001; IL-33: from 2.57 ± 1.3 pg/ml to 5.7 ± 3.1 pg/ml, p < 0.001). Conclusions. CRSwNP epithelial cells release TSLP and IL-25 when stimulated by poly(I:C) but not by DP or AF, suggesting that viral infection may contribute to maintain and amplify the T2 immune response seen in CRSwNP.

show abstract

“…IL-1β and tumor necrosis factor (TNF)-α regulate TSLP transcript expression in an nuclear factor-kappa B (NF-κB)-dependent manner 39. Several researchers have demonstrated that TSLP mRNA is overexpressed in eosinophilic NP and associated with Th2 inflammation 404142. TSLP induces the differentiation of naïve T cells into effector Th2 cells via enhancement of OX40 ligand (OX40L)-OX40 axis on the interaction between dendritic cells and CD4 T cells 43.…”

Section: Pathogenesis and Endotypes Of Crsmentioning

confidence: 99%

Emerging Endotypes of Chronic Rhinosinusitis and Its Application to Precision Medicine

Kim

Cho

2017

Allergy Asthma Immunol Res

View full text Add to dashboard Cite

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with various underlying pathophysiologic mechanisms which translate to endotypes, in contrast to clinical phenotypes or histological subtypes. Defining endotypes can help clinicians predict disease prognosis, select subjects suitable for a specific therapy, and assess risks for comorbid conditions, including asthma. Therefore, with recent advancement of biologicals in CRS clinical trials, endotyping can be a breakthrough in treating recalcitrant CRS. CRS is caused by dysregulated immunologic responses to external stimuli, which induce various inflammatory mediators from inflammatory cells, including innate lymphoid cells (ILCs) and T lymphocytes as well as epithelial cells. Thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, which are mainly secreted by epithelial cells in response to external stimuli, act on type 2 ILCs and T helper 2 (Th2) cells, inducing IL-4, IL-5, and IL-13. Local immunoglobulin E (IgE) production is also a signature event in nasal polyps (NP). These inflammatory mediators are novel potential therapeutic targets for recalcitrant CRS. This article reviews recent publications regarding endotypes and endotype-based therapeutic strategies in CRS and NP.

show abstract

Eosinophilic inflammation of chronic rhinosinusitis with nasal polyps is related to OX40 ligand expression

Cited by 18 publications

References 30 publications

Immunopathology of chronic rhinosinusitis

Immunopathology of chronic rhinosinusitis

Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps

Emerging Endotypes of Chronic Rhinosinusitis and Its Application to Precision Medicine

Contact Info

Product

Resources

About