IL-9 Induces VEGF Secretion from Human Mast Cells and IL-9/IL-9 Receptor Genes Are Overexpressed in Atopic Dermatitis

Sismanopoulos, Nikolaos; Delivanis, Danae A.; Alysandratos, Konstantinos D.; Angelidou, Asimenia; Vasiadi, Magdalini; Therianou, Anastasia; Theoharides, Theoharis C.

doi:10.1371/journal.pone.0033271

Cited by 64 publications

(55 citation statements)

References 51 publications

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“…TARC levels were reduced in all 4 study patients in the omalizumab-treated group (between 60 and 80% in 3 patients; see table 1) compared to the placebo-treated group. IL-9, a cytokine secreted in affected skin areas of AD patients that also potentiates IL-4-mediated IgE production from B cells [9], was also decreased in the omalizumab-treated group (by 50–75%), with increasing levels noted in the majority of patients in the placebo-treated group over the course of the study (data not shown). Serum levels of IL-10, a tolerogenic cytokine produced by T regulatory cells, was increased between 80 and 100% in omalizumab-treated, but not in the placebo-treated study patients (see table 1).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Immunologic Effects of Omalizumab in Children with Severe Refractory Atopic Dermatitis: A Randomized, Placebo-Controlled Clinical Trial

Iyengar

Hoyte²,

Loza³

et al. 2013

Int Arch Allergy Immunol

125

124

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Background: Severe refractory atopic dermatitis (AD) is a chronic, debilitating condition that is associated with elevated serum immunoglobulin E (IgE) levels. Thymic stromal lymphopoietin (TSLP), thymus and activation-regulated chemokine (TARC) and OX40 ligand (OX40L) are important immunologic factors involved in the pathogenesis of AD. Omalizumab, an anti-IgE antibody indicated for use in allergic asthma, is implicated in regulating allergen presentation by dendritic cells and the T cell response during the effector phases of allergic disease. We investigated if anti-IgE therapy modulates the allergen-specific responses mediated by the TSLP pathway in young patients with severe refractory AD. Methods: This was a randomized, double-blind, placebo-controlled study of 8 patients between the ages of 4 and 22 years (mean = 11.6 years) with severe refractory AD (clinical trials.gov NCT01678092). Serum IgE ranged from 218 to 1,890 (mean = 1,068 IU/ml). Subjects received omalizumab (n = 4) or placebo (n = 4) every 2-4 weeks over 24 weeks using a regimen extrapolated from the package insert. TSLP, TARC, OX40L and other cytokines involved in AD were measured by using cytometric bead arrays. Results: All patients receiving omalizumab had strikingly decreased levels of TSLP, OX40L, TARC (involved in Th2 polarization) and interleukin (IL)-9 compared to placebo. In addition, there was a marked increase in IL-10, a tolerogenic cytokine, in the omalizumab-treated group. Patients on anti-IgE therapy had an improvement in clinical outcomes as measured by the SCORAD system; however, these effects were comparable to improvements in the control group. Conclusions: Anti-IgE therapy with omalizumab decreases levels of cytokines that are involved in Th2 polarization and allergic inflammation, including TSLP, TARC and OX40L.

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Section: Resultsmentioning

confidence: 99%

“…Therefore, TSLP plays a critical role in promoting Th2-mediated allergic inflammation in AD. Other cytokines involved in the pathogenesis of AD include interleukin (IL)-9, which is significantly increased in lesional skin areas of AD patients and other allergic inflammatory diseases, like asthma [9]. …”

Section: Introductionmentioning

confidence: 99%

Immunologic Effects of Omalizumab in Children with Severe Refractory Atopic Dermatitis: A Randomized, Placebo-Controlled Clinical Trial

Iyengar

Hoyte²,

Loza³

et al. 2013

Int Arch Allergy Immunol

125

124

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“…IL-9 induces the release of VEGF from human mast cells and may have a role in atopic dermatitis (27). Few mast cells have been described as participating in the vessel wall lesions (28).…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory and anti-inflammatory T cells in giant cell arteritis

et al. 2017

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Giant cell arteritis is an autoimmune disease defined by explicit tissue tropism to the walls of medium and large arteries. Pathognomic inflammatory lesions are granulomatous in nature, emphasizing the functional role of CD4 T cells and macrophages. Evidence for a pathogenic role of antibodies and immune complexes is missing. Analysis of T cell populations in giant cell arteritis, both in the tissue lesions and in the circulation, has supported a model of broad, polyclonal T cell activation, involving an array of functional T cell lineages. The signature of T cell cytokines produced by vasculitic lesions is typically multifunctional, including IL-2, IFN-γ, IL-17, IL-21, and GM-CSF, supportive for a general defect in T cell regulation. Recent data describing the lack of a lymph node-based population of anti-inflammatory T cells in giant cell arteritis patients offers a fresh look at the immunopathology of this vasculitis. Due to defective CD8+NOX2+ regulatory T cells, giant cell arteritis patients appear unable to curtail clonal expansion within the CD4 T cell compartment, resulting in wide-spread CD4 T cell hyperimmunity. Why unopposed expansion of committed CD4 effector T cells would lead to invasion of the walls of medium and large arteries needs to be explored in further investigations.

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“…As IL-9 and its receptor are significantly elevated locally in patients with atopic asthma and atopic dermatitis, these results suggest a pathological link between IL-9 and mast cells in the development of atopic diseases (Shimbara et al, 2000;Sismanopoulos et al, 2012).…”

Section: Il-9mentioning

confidence: 76%