IL-4 and IL-13

The role of IL-4 and IL-13 signalling in type 2 inflammation

IL-4 and IL-13 signalling

Type 2 inflammation plays an important role in uncontrolled asthma, contributing to increased exacerbations and decreased lung function.1-3

IL-4 and IL-13 play key upstream roles in the pathophysiology of asthma caused by allergic and eosinophilic inflammation.1,2

At the tissue level, eosinophils trafficked by IL-4 and IL-13 to sites of inflammation contribute to airway remodeling and potential loss of lung function. IL-13 also affects smooth muscle cells contributing to bronchoconstriction that leads to airway hyperresponsiveness (AHR).

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Adapted from Robinson D et al. 2017.1

 

IL-4 and IL-13 work upstream and have key effects downstream1,3
IL-13 and IL-4 activate via a common heterodimeric receptor complex expressed by several immune, inflammatory and airway cells, which may explain their overlapping roles in type 2 inflammation in asthma.

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  • IL-4 acts as a regulatory cytokine1
  • IL-4 drives Th2 cell differentiation
  • IL-4 binds to the IL-4Rα receptor expressed on:
    • T helper cells
    • Eosinophils
    • Mast cells
    • B cells
    • Bronchial epithelium
    • Endothelium
    • Airway smooth muscle cells

IL-13 acts as an effector cytokine1

  • IL-13 has a multifunctional role in asthma pathogenesis, including B-cell isotype switching, mucus hypersecretion, goblet cell hyperplasia, subepithelial fibrosis and airway hypersensitivity
  • IL-13 receptors are expressed on:
    • Airway smooth muscle cells
    • Airway epithelial cells

References

  1. 1.Robinson D et al. Clin Exp Allergy 2017; 47(2): 161–75.
  2. 2.Hammad H and Lambrecht BN. Nat Rev Immunol 2008; 8(3): 193–204.
  1. 3.Australian Approved Product Information for DUPIXENT (dupilumab). 6 October 2020.