A dysregulated type 2 immune response drives inflammation AND CONTRIBUTES
TO clinical manifestations
of CSU1,2

Mast cell activation and degranulation are central to the pathophysiology of CSU3

Mast cell activation
Mast cells can be activated
through multiple pathways1,3-5
cell activation
Mast cell degranulation
Mast cell degranulation leads to release of histamine and other mediators, which promotes vasodilation and increased vascular permeability1,3-5
cell degranulation

Histamine and other mediators recruit type 2 lymphocytes, eosinophils, basophils, and neutrophils to the skin1,6,7

The recruitment of immune cells to the site of mast cell degranulation further amplifies the inflammatory response and promotes the persistence of1,2,6-8:

Wheals
Angioedema

Type 2 cytokines contribute to disease chronicity in CSU

IL-4
  • Promotes the differentiation of Th0 cells into Th2 cells, which produce type 2 cytokines, continually amplifying inflammatory dysregulation in a positive feedback loop9,10
IL-4
IL-13
  • Enhance IgE and IgG production2,9-11
  • Increase expression of FcεRI on mast cells2,9,10,12
  • Increase recruitment of type 2 inflammatory cells11,13
  • May sensitize neurons to the effects of stimuli14
IL-5
  • Regulates eosinophils, which may promote mast cell maturation and degranulation11,15

The bidirectional relationship between immune cells and sensory neurons may further perpetuate the cycle of inflammation in CSU16

IL-4 and IL-13 can amplify
the inflammatory
response in CSU1,4,9,11,20

FcεRI, fragment constant (of Ig) receptor; IL-4R, interleukin-4 receptor; MRGPRX2, Mas-related G protein-coupled receptor-X2.

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