Innate Immune Responses in Asthma

Key Cellular Components of Innate Immunity in Asthma

Epithelial cells function as the first line of defense and sentinel cells that detect environmental triggers, according to the American Academy of Allergy, Asthma, and Immunology 1, 2
Epithelial cells release alarmins (IL-25, IL-33, TSLP) upon exposure to allergens, viruses, or pollutants that activate downstream inflammatory pathways, as noted by the European Respiratory Society 3
Mast cells release inflammatory mediators (histamine, leukotrienes, prostaglandin D2) upon activation, contributing to immediate bronchoconstriction and airway hyperresponsiveness, as stated by the American College of Allergy, Asthma, and Immunology 1
Eosinophils are key effector cells in type 2 inflammation, recruited by IL-5 produced by TH2 cells and type 2 innate lymphoid cells (ILC2s), according to the American Thoracic Society 5
Neutrophils are predominant in certain asthma phenotypes, such as severe asthma, and are recruited through IL-8 and IL-17-dependent pathways, as noted by the European Respiratory Society 1, 2, 3

Protease-activated receptors (PAR2) on epithelial cells and inflammatory cells can be activated by allergen-derived proteases, promoting inflammatory cell recruitment and cytokine production, as stated by the American Academy of Allergy, Asthma, and Immunology 4, 6
The hygiene hypothesis proposes that reduced early-life exposure to certain infections shifts immune responses toward TH2 predominance, according to the American College of Allergy, Asthma, and Immunology 1, 2

IL-5 drives eosinophil development, recruitment, and survival, as noted by the European Respiratory Society 5
IL-17 produced by TH17 cells and type 3 ILCs stimulates neutrophilic inflammation, and TNF-α contributes to mixed inflammatory responses in severe asthma, according to the American Thoracic Society 3

Anti-IL-5 therapies (mepolizumab, reslizumab, benralizumab) target eosinophilic inflammation, as stated by the American College of Allergy, Asthma, and Immunology 5
CRTH2 antagonists block PGD2 signaling, potentially affecting both TH2 cells and ILC2s, according to the European Respiratory Society 5
Anti-TSLP therapies show promise in reducing asthma exacerbations, as noted by the American Thoracic Society 3

Non-type 2 asthma, often neutrophil-predominant or paucigranulocytic, may be triggered by infections, cigarette smoke, or pollution rather than allergens, and is more difficult to treat with conventional therapies, according to the European Respiratory Society 3

Asthma is highly heterogeneous, with different inflammatory patterns requiring different treatment approaches, as stated by the American Academy of Allergy, Asthma, and Immunology 1
Animal models of asthma may not fully recapitulate human disease complexity, according to the European Respiratory Journal 7
Environmental factors significantly influence innate immune responses in asthma, making standardized approaches challenging, as noted by the American College of Allergy, Asthma, and Immunology 2