Th9 Cells in Allergic Disease

Angkasekwinai, Pornpimon

doi:10.1007/s11882-019-0860-8

Cited by 45 publications

(32 citation statements)

References 97 publications

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“…We here show a clear shift in the overall T‐cell responses from IL5, IL13 and IL9 towards enhanced IFNγ secretion during the treatment, suggesting a change in the balance between Th2/Th9 and Th1 T‐cell responses. This shift in balance away from the IgE stimulating Th2 and Th9 phenotypes 30‐32 towards the Th1 phenotype suggests a less allergy‐prone T‐cell phenotype 33 . A preliminary comparison of these T‐cell responses did not point towards differences between TF and TS (data not shown).…”

Section: Discussionmentioning

confidence: 93%

A pilot study towards the immunological effects of omalizumab treatment used to facilitate oral immunotherapy in peanut‐allergic adolescents

et al. 2020

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Anti‐IgE treatments, such as omalizumab, have shown promising effects in allergy treatment. Our previous work has shown that individualized omalizumab treatment (OT) allows a safe initiation and rapid up‐dosing of peanut oral immunotherapy (OIT) in peanut‐allergic adolescents. However, the broader immunological effects of this OT are incompletely understood. In this pilot study, we longitudinally followed the total B‐ and T‐cell immunity during OT, using flow cytometry, ELISpot and ELISA. Peripheral blood mononuclear cells (PBMCs) and plasma were collected from participants (n = 17) at several timepoints during treatment, before starting OT (baseline), prior to starting OIT during OT (start OIT) and at maintenance dose OIT prior to OT reduction (maintenance). OT did not affect the total B‐cell compartment over treatment time, but our results suggest an association between the OT dosage scheme and the B‐cell compartment. Further, in vitro polyclonal T‐cell activation at the different timepoints suggests a cytokine skewing towards the Th1 phenotype at the expense of Th2‐ and Th9‐related cytokines during treatment. No differences in the frequencies or phenotype of regulatory T cells (Tregs) over treatment time were observed. Finally, plasma chemokine levels were stable over treatment time, but suggest elevated gut homing immune responses in treatment successes during the treatment as compared to treatment failures. The novel and explorative results of this pilot study help to improve our understanding on the immunological effects of OT used to facilitate OIT and provide guidance for future immunological investigation in large clinical trials.

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Section: Discussionmentioning

confidence: 93%

A pilot study towards the immunological effects of omalizumab treatment used to facilitate oral immunotherapy in peanut‐allergic adolescents

et al. 2020

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“…IL-27 also promotes the development of IL-10, producing T-bet + CXCR3 + Treg cells (41). IL-4 and TGF-β elicit naïve CD4 + T cells differentiation to Th9 cells, which express the transcription factor PU.1 and secrete large amounts of IL-9 that contribute to mast cell activation, induction of allergic reactions, and immune responses to intestinal helminth infections (42). IL-27 inhibits the development of Th9 cells (43).…”

Section: Effects Of Il-27 On the Adaptive Immune Systemmentioning

confidence: 99%

Interleukin-27 Functional Duality Balances Leishmania Infectivity and Pathogenesis

et al. 2020

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IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy.

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“…The production of Th2 cytokines also leads to the recruitment of innate effector cells, including mast cells, basophils, and eosinophils, as well as to isotype switching of B cell-secreted IgG to allergen-specific IgE [19]. Additionally, Th9 cells, a recently identified Th cell subset characterized by high levels of IL-9, exacerbate allergic airway inflammation (AAI), predominantly through activation of mast cell functions [20,21]. More specifically, experimental studies have shown that IL-9 production by Th9 cells and by type 2 innate lymphoid cells (ILC2s) enhances the production of IL-2 by mast cells, leading to further expansion of ILC2s, which activate Th9 cells, in a positive feedback loop [22].…”

Section: Severe Asthma Pathogenesismentioning

confidence: 99%

Targeting NLRP3 Inflammasome Activation in Severe Asthma

Theofani

Semitekolou

Morianos

et al. 2019

JCM

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Severe asthma (SA) is a chronic lung disease characterized by recurring symptoms of reversible airflow obstruction, airway hyper-responsiveness (AHR), and inflammation that is resistant to currently employed treatments. The nucleotide-binding oligomerization domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome is an intracellular sensor that detects microbial motifs and endogenous danger signals and represents a key component of innate immune responses in the airways. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent release of the pro-inflammatory cytokines IL-1β and IL-18 as well as pyroptosis. Accumulating evidence proposes that NLRP3 activation is critically involved in asthma pathogenesis. In fact, although NLRP3 facilitates the clearance of pathogens in the airways, persistent NLRP3 activation by inhaled irritants and/or innocuous environmental allergens can lead to overt pulmonary inflammation and exacerbation of asthma manifestations. Notably, administration of NLRP3 inhibitors in asthma models restrains AHR and pulmonary inflammation. Here, we provide an overview of the pathophysiology of SA, present molecular mechanisms underlying aberrant inflammatory responses in the airways, summarize recent studies pertinent to the biology and functions of NLRP3, and discuss the role of NLRP3 in the pathogenesis of asthma. Finally, we contemplate the potential of targeting NLRP3 as a novel therapeutic approach for the management of SA.

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Th9 Cells in Allergic Disease

Cited by 45 publications

References 97 publications

A pilot study towards the immunological effects of omalizumab treatment used to facilitate oral immunotherapy in peanut‐allergic adolescents

A pilot study towards the immunological effects of omalizumab treatment used to facilitate oral immunotherapy in peanut‐allergic adolescents

Interleukin-27 Functional Duality Balances Leishmania Infectivity and Pathogenesis

Targeting NLRP3 Inflammasome Activation in Severe Asthma

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