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Figure 2. Mechanisms of T2-high asthma. Eos, Eosinophils; GATA3, GATA3 transcription factor; MC, endotypes and immune cells in severe asthma
mast cells/basophils; SM, smooth muscle cells; Th, T helper cells. Adapted from Corren, 2019.
transcription factor GATA-3. Th2 cells then fibroblasts. Very important from the thera-
stimulate type 2 immunity through the se- peutic target, IL-5 plays a pivotal role for eo-
cretion of the cytokines IL-4, IL-5, and IL- sinophils (differentiation and survival)5,7,11,13.
13. Importantly, both IL-4, as well as IL-13,
utilize a common IL-4Rα chain. IL-5 plays While the role of mast cells degranula-
a pivotal role in promoting the differentiation tion in acute asthma exacerbation is well es-
and maturation of eosinophils, as well as their tablished especially in allergen driven ex-
subsequent mobilization and survival. Fur- acerbations, the functional significance of
thermore, T2 cytokines have effects on gob- basophils in asthma has recently gained at-
let cells (mucus), fibrogenic functions (remod- tention. Notably, it was shown that basophils
elling), and hyperresponsiveness5,7,11. have been recruited in the bronchial walls of
T2-high asthma. Moreover, it is well known
Eosinophils are the hallmark cell type as- that in humans basophils are one of the major
sociated with T2-high asthma and have plei- producers of IL-4 and can thus directly mod-
otropic effects on various inflammatory cells. ulate T2 inflammation. IgEs, which on mast
Upon stimulation, they release a myriad of cells and basophils through FcεRI mediate
inflammatory mediators chemokines, and cy- immediate hypersensitivity response to aller-
tokines including IL-5, IL-13, eotaxin, cystei- gens, can also facilitate and modulate antigen
nyl leukotriene (CysLT), major basic protein presentation by dendritic cells and response
(MBP), eosinophil peroxidase (EPX), and eo- to viruses. Additionally, recent data strongly
sinophil cationic protein (ECP). CysTL is a suggest that an altered functional subtype of
potent bronchoconstrictor that acts in syner- mast cells may have greater potential to gen-
gy with IL-33 and further drives the self-am- erate PGD2. These PGD2-high mast cells
plifying loop that characterizes T2 inflam- strongly predict poorly controlled T2-high
mation. Eosinophils also activate bronchial
Figure 2. Mechanisms of T2-high asthma. Eos, Eosinophils; GATA3, GATA3 transcription factor; MC, endotypes and immune cells in severe asthma
mast cells/basophils; SM, smooth muscle cells; Th, T helper cells. Adapted from Corren, 2019.
transcription factor GATA-3. Th2 cells then fibroblasts. Very important from the thera-
stimulate type 2 immunity through the se- peutic target, IL-5 plays a pivotal role for eo-
cretion of the cytokines IL-4, IL-5, and IL- sinophils (differentiation and survival)5,7,11,13.
13. Importantly, both IL-4, as well as IL-13,
utilize a common IL-4Rα chain. IL-5 plays While the role of mast cells degranula-
a pivotal role in promoting the differentiation tion in acute asthma exacerbation is well es-
and maturation of eosinophils, as well as their tablished especially in allergen driven ex-
subsequent mobilization and survival. Fur- acerbations, the functional significance of
thermore, T2 cytokines have effects on gob- basophils in asthma has recently gained at-
let cells (mucus), fibrogenic functions (remod- tention. Notably, it was shown that basophils
elling), and hyperresponsiveness5,7,11. have been recruited in the bronchial walls of
T2-high asthma. Moreover, it is well known
Eosinophils are the hallmark cell type as- that in humans basophils are one of the major
sociated with T2-high asthma and have plei- producers of IL-4 and can thus directly mod-
otropic effects on various inflammatory cells. ulate T2 inflammation. IgEs, which on mast
Upon stimulation, they release a myriad of cells and basophils through FcεRI mediate
inflammatory mediators chemokines, and cy- immediate hypersensitivity response to aller-
tokines including IL-5, IL-13, eotaxin, cystei- gens, can also facilitate and modulate antigen
nyl leukotriene (CysLT), major basic protein presentation by dendritic cells and response
(MBP), eosinophil peroxidase (EPX), and eo- to viruses. Additionally, recent data strongly
sinophil cationic protein (ECP). CysTL is a suggest that an altered functional subtype of
potent bronchoconstrictor that acts in syner- mast cells may have greater potential to gen-
gy with IL-33 and further drives the self-am- erate PGD2. These PGD2-high mast cells
plifying loop that characterizes T2 inflam- strongly predict poorly controlled T2-high
mation. Eosinophils also activate bronchial
