[The immunopathology of asthma]

Area of Science:

• Immunology
• Pulmonology
• Allergy and Asthma Research

Background:

• Type 2 (T2) high asthma is characterized by T2 markers like eosinophilia, driven by type 2 innate lymphoid cells (ILC2) and T helper 2 (Th2) cells.
• Epithelial-derived alarmins (IL-33, TSLP, IL-25, TL1A) are central to T2 high asthma pathogenesis, influencing dendritic cells and ILC2.
• These alarmins, produced in response to environmental triggers, initiate immune responses contributing to asthma pathology.

Purpose of the Study:

• To elucidate the key cellular and molecular drivers of T2 high asthma.
• To highlight the role of alarmins and T2-associated cytokines in asthma immunopathology.
• To identify the distinct immunological pathways potentially underlying T2 low asthma.

Main Methods:

• Review of current literature on T2 high and T2 low asthma.
• Analysis of cellular mechanisms involving ILC2, Th2 cells, and epithelial alarmins.
• Exploration of alternative pathways in T2 low asthma, including IL-22/IL-17 and inflammasome activation.

Main Results:

• Alarmins IL-33, TSLP, IL-25, and TL1A activate ILC2 and dendritic cells, driving T2 high asthma.
• Th2 cells and ILC2 produce cytokines that cause eosinophilia, mast cell activation, goblet cell hyperplasia, and fibrosis.
• T2 low asthma appears linked to IL-22/IL-17 cytokines and inflammasome activation, distinct from T2 high pathways.

Conclusions:

• Alarmins and T2-associated cells are critical in T2 high asthma, leading to airway hyperresponsiveness and remodeling.
• The mechanisms of T2 low asthma remain less understood, suggesting alternative inflammatory pathways.
• Further research into T2 low asthma etiology is necessary for developing targeted therapies.