Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses

Hua Sun1, J Morgan Knight2, Yi-Dong Li1

  • 1Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School of The University of Texas Health Science Center at Houston, Houston, Tex; Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Tex.

Abstract

Insights

Allergic fungal rhinosinusitis (AFRS) involves downregulated antimicrobial peptides (AMPs) due to a defect in IL-6/STAT3 signaling, impacting T helper cell differentiation and leading to reduced antifungal defense.

Area of Science:

  • Immunology
  • Molecular Biology
  • Otorhinolaryngology

Background:

  • Allergic fungal rhinosinusitis (AFRS) shows significantly lower expression of histatin 1 (HTN1), a key antimicrobial peptide (AMP).
  • This downregulation is a distinguishing genetic feature when comparing AFRS with chronic rhinosinusitis with nasal polyps (CRSwNP).

Purpose of the Study:

  • To investigate the underlying molecular mechanisms responsible for the reduced expression of HTN1 in AFRS.
  • To understand the role of T helper cell subsets and signaling pathways in AFRS pathogenesis.

Main Methods:

  • Quantitative RT-PCR to measure AMP expression.
  • Fungistasis assays to assess antifungal activity of sinus secretions.
  • Flow cytometry to analyze T helper 17 (TH17)/T helper 22 (TH22) cells and signal transducer and activator of transcription (STAT) signaling.

Main Results:

  • AFRS patients exhibit decreased AMP expression and reduced antifungal activity in sinus secretions.
  • A deficiency in IL-22 and IL-22-producing T cells was observed in the sinus mucosa of AFRS patients.
  • In vitro studies revealed a defect in IL-6/STAT3 signaling crucial for TH17/TH22 cell differentiation, although circulating TH17 cells were normal.

Conclusions:

  • AFRS is characterized by a specific defect in IL-6-dependent STAT3 activation, impairing TH17/TH22 differentiation.
  • This signaling defect results in localized deficiency of IL-17/IL-22 cytokines and reduced AMP expression in the sinus mucosa.
  • Therapeutic strategies aimed at boosting airway AMP production may be beneficial for AFRS treatment.

Related Concept Videos

Allergic Reactions02:06

Allergic Reactions

Overview
27.3K
Hypersensitivities01:30

Hypersensitivities

Hypersensitivity, also known as a hypersensitivity reaction or allergic reaction, is a condition where the body's immune system reacts abnormally to a foreign substance. Such substances, that cause hypersensitivity are referred to as an allergen, could be something typically harmless to most people, like pollen or certain foods.
Types of Hypersensitivities
Hypersensitivity reactions are categorized into four types: Type 1, Type 2, Type 3, and Type 4. Each type has a distinct mechanism...
573
Asthma: Pathogenesis and Management01:20

Asthma: Pathogenesis and Management

Asthma is a chronic pulmonary condition involving inflammation of the airways, hyper-reactivity, and reversible obstruction of the airways. This condition can significantly impact a person's quality of life, making breathing difficult and leading to distressing symptoms.
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
381
Asthma-II: Pathophysiology and Classification01:26

Asthma-II: Pathophysiology and Classification

Asthma is a prevalent chronic respiratory condition marked by inflammation and hyperresponsiveness of the airways. Its pathophysiology involves complex interactions among inflammatory pathways, immune responses, and neural mechanisms.
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
2.6K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
990
Asthma-I: Introduction01:29

Asthma-I: Introduction

Asthma is a chronic respiratory ailment that requires careful management due to its varying symptoms and influencing factors. It is characterized by airway inflammation, bronchial hyperresponsiveness, and reversible airflow obstruction, leading to symptoms like wheezing, shortness of breath, chest tightness, and coughing. The symptom frequency and intensity may vary considerably over time. It is also linked to immune system responses to allergens and irritants, highlighting the complex...
2.6K