From the Guidelines
A Th2-dominant microenvironment is characterized by the predominance of T helper 2 (Th2) cells and their associated cytokines, including IL-4, IL-5, IL-9, and IL-13, which promote antibody-mediated immunity and are associated with allergic conditions, asthma, and certain parasitic infections. This environment is typically marked by increased IgE production, eosinophil activation, and mast cell degranulation, leading to symptoms such as inflammation, mucus production, and airway hyperresponsiveness in asthma 1. The Th2-dominant microenvironment represents a deviation from immune homeostasis, where Th1 and Th2 responses are normally balanced.
Key Characteristics of Th2-Dominant Microenvironment
- Increased production of IL-4, IL-5, IL-9, and IL-13
- Promotion of antibody-mediated immunity, particularly IgE production
- Activation of eosinophils and mast cells
- Association with allergic conditions, asthma, and certain parasitic infections
- Deviation from immune homeostasis, with an imbalance towards Th2 dominance
Clinical Implications
Understanding the Th2-dominant microenvironment is crucial for developing targeted therapies for allergic and inflammatory conditions. Treatments often aim to restore balance by suppressing excessive Th2 activity or enhancing counterregulatory mechanisms 1. The identification of subphenotypes, such as Th2-high and Th2-low asthma, can help tailor treatment approaches to specific patient populations, improving treatment outcomes and reducing morbidity and mortality 1.
Relevance to Asthma
In asthma, the Th2-dominant microenvironment is characterized by eosinophilic airway inflammation and allergic sensitization, primarily driven by IgE and IL-4, IL-5, and IL-13 1. This understanding has enabled the development of novel biological therapies that have proven effective in treating severe asthma. However, the management of asthma exacerbations remains a major issue, with significant variation in guideline recommendations and clinical practice affecting diagnostic and treatment decisions 1.
From the Research
Definition of T-helper 2 (Th2)-dominant microenvironment
- A T-helper 2 (Th2)-dominant microenvironment refers to a specific type of immune environment where Th2 cells play a crucial role in orchestrating protective type 2 immune responses [(2,3,4,5,6)].
- This microenvironment is characterized by the presence of Th2 cells, which produce cytokines such as IL-4, IL-5, and IL-13, and interact with other immune cells, such as dendritic cells and epithelial cells [(2,3,4,5,6)].
Characteristics of Th2-dominant microenvironment
- Th2-dominant microenvironments are often associated with allergic inflammation and immune responses against helminths [(2,3,4,5,6)].
- The formation of Th2 macro-clusters, which are integrin-mediated and promote localized cytokine exchange among T cells, is a key feature of Th2-dominant microenvironments 2.
- The site of skin sensitization can influence the formation of Th2-dominant microenvironments, with different dermal tissues exhibiting distinct activation states of migratory cDC2 2.
Role of Th2 cells in Th2-dominant microenvironment
- Th2 cells play a critical role in initiating and maintaining Th2 responses in vivo, and their differentiation is influenced by various factors, including cytokines, dendritic cells, and epithelial cells [(3,4,5,6)].
- Th2 cells can evoke immunoglobulin class-switch to IgE and generate IL-4, IL-5, and IL-13, which contribute to eosinophilia, IgE class-switch, and epithelial barrier activation 4.
- The regulation of Th2 cell responses is complex and involves the integration of diverse polarizing cues by cellular sensors and molecular programs 3.