Page 22 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 22
infection in humans. Recently, studies have secretory products, serine proteases tryptase,
been initiated to elucidate the effects of asth- chymase, and carboxy-peptidase, can interact
severe asthma forum 1: severe asthma - basic and clinical views ma treatment on ILC2s and to modulate with various cell types and direct their activ-
ILC2s as a potential treatment option for ity via protease-activated receptors and other
asthma as ILC2s may contribute to steroid re- processes4. On the other hand, the function-
sistance and persistent airway pathology. Fur- al significance of basophils in the pathogene-
ther studies using anti-IL5 and IL4/13 bio- sis of asthma has gained attention only recent-
logics likely will provide useful information ly. Similarly, as mast cells, IgEs on basophils
to dissect the roles of ILC2s and innate type through FcεRI mediate immediate hypersen-
2 responses in the pathophysiology of asth- sitivity in response to allergens, and can also
ma and, at the same time, will help to develop facilitate and modulate antigen presentation
novel treatment strategies for asthma by tar- by dendritic cells and response to viruses. Ba-
geting ILC2s3. Further studies are also need- sophils are recruited in the bronchial walls of
ed to elucidate the possible role of ILC1s and T2-high asthma. Basophils and eosinophils
ILC3 responses in asthma. appear to be closely linked by directly or in-
directly influencing each other since they are
Mast Cells and Basophils responsive to similar cytokines and chemok-
ines10. Basophils activation leads to the release
The evidence that mast cells degranula- of immunoregulatory and effector mediators,
tion followed by the release of various medi- including IL-4 and IL-13, histamine, and
ators represent important contributors to the LTC4. Moreover, it is well known that human
pathogenesis of asthma is strong. Mast cells basophils are one of the major producers of
normally reside in the lungs, and on activation IL-4 and can thus directly modulate T2 in-
by IgE-dependent or other mechanisms, they flammation4,5,7,11,13.
can release a diverse spectrum of mediators
that in turn can rapidly induce local effects The pathophysiologic mechanisms driv-
on blood vessels, nerves, and mucous glands, ing corticosteroid insensitivity and severe
as well as on epithelial cells, airway smooth asthma are still unclear and evidence sug-
muscle cells, and immune cells4. Among the gests that mast cells and basophils might have
mast cells secreted mediators histamine, pros- a role in it. In vitro studies using various cell
taglandin (PG) D2, and leukotriene (LT) C4 types showed that different mediators pro-
are capable of inducing bronchoconstriction, duced by activated mast cells and/or baso-
mucus secretion, and mucosal oedema, all phils, including cytokines, can interfere with
asthma characteristics. Additionally, recent the therapeutic action of corticosteroids. Me-
data strongly suggest that an altered function- diators released by activated mast cells have
al subtype of mast cells may have greater po- been shown to decrease the anti-inflammato-
tential to generate PGD2. These PGD2-high ry action of glucocorticoids in airway smooth
mast cells strongly predict poorly controlled muscle cells by reducing the expression of an-
T2-high asthma and are associated with ti-inflammatory genes. Mast cells infiltra-
more severe disease (targeting CRTH2)5,7,11,13. tion and interactions have been described in
Besides, mast cells also synthesize and se- different compartments of the airways, in-
crete a large number of proinflammatory cy- cluding epithelium, submucosa and airway
tokines (including IL-4, IL-5, and IL-13), smooth muscle. Therefore, mast cells‘ airway
which regulate both IgE synthesis and the infiltration, release of mediators and interac-
development of eosinophilic inflammation, tion with lung structural cells may contrib-
and several profibrogenic cytokines, includ- ute to the corticosteroid insensitivity in severe
ing TGF-β. Furthermore, major mast cells‘ asthma2,4.
been initiated to elucidate the effects of asth- chymase, and carboxy-peptidase, can interact
severe asthma forum 1: severe asthma - basic and clinical views ma treatment on ILC2s and to modulate with various cell types and direct their activ-
ILC2s as a potential treatment option for ity via protease-activated receptors and other
asthma as ILC2s may contribute to steroid re- processes4. On the other hand, the function-
sistance and persistent airway pathology. Fur- al significance of basophils in the pathogene-
ther studies using anti-IL5 and IL4/13 bio- sis of asthma has gained attention only recent-
logics likely will provide useful information ly. Similarly, as mast cells, IgEs on basophils
to dissect the roles of ILC2s and innate type through FcεRI mediate immediate hypersen-
2 responses in the pathophysiology of asth- sitivity in response to allergens, and can also
ma and, at the same time, will help to develop facilitate and modulate antigen presentation
novel treatment strategies for asthma by tar- by dendritic cells and response to viruses. Ba-
geting ILC2s3. Further studies are also need- sophils are recruited in the bronchial walls of
ed to elucidate the possible role of ILC1s and T2-high asthma. Basophils and eosinophils
ILC3 responses in asthma. appear to be closely linked by directly or in-
directly influencing each other since they are
Mast Cells and Basophils responsive to similar cytokines and chemok-
ines10. Basophils activation leads to the release
The evidence that mast cells degranula- of immunoregulatory and effector mediators,
tion followed by the release of various medi- including IL-4 and IL-13, histamine, and
ators represent important contributors to the LTC4. Moreover, it is well known that human
pathogenesis of asthma is strong. Mast cells basophils are one of the major producers of
normally reside in the lungs, and on activation IL-4 and can thus directly modulate T2 in-
by IgE-dependent or other mechanisms, they flammation4,5,7,11,13.
can release a diverse spectrum of mediators
that in turn can rapidly induce local effects The pathophysiologic mechanisms driv-
on blood vessels, nerves, and mucous glands, ing corticosteroid insensitivity and severe
as well as on epithelial cells, airway smooth asthma are still unclear and evidence sug-
muscle cells, and immune cells4. Among the gests that mast cells and basophils might have
mast cells secreted mediators histamine, pros- a role in it. In vitro studies using various cell
taglandin (PG) D2, and leukotriene (LT) C4 types showed that different mediators pro-
are capable of inducing bronchoconstriction, duced by activated mast cells and/or baso-
mucus secretion, and mucosal oedema, all phils, including cytokines, can interfere with
asthma characteristics. Additionally, recent the therapeutic action of corticosteroids. Me-
data strongly suggest that an altered function- diators released by activated mast cells have
al subtype of mast cells may have greater po- been shown to decrease the anti-inflammato-
tential to generate PGD2. These PGD2-high ry action of glucocorticoids in airway smooth
mast cells strongly predict poorly controlled muscle cells by reducing the expression of an-
T2-high asthma and are associated with ti-inflammatory genes. Mast cells infiltra-
more severe disease (targeting CRTH2)5,7,11,13. tion and interactions have been described in
Besides, mast cells also synthesize and se- different compartments of the airways, in-
crete a large number of proinflammatory cy- cluding epithelium, submucosa and airway
tokines (including IL-4, IL-5, and IL-13), smooth muscle. Therefore, mast cells‘ airway
which regulate both IgE synthesis and the infiltration, release of mediators and interac-
development of eosinophilic inflammation, tion with lung structural cells may contrib-
and several profibrogenic cytokines, includ- ute to the corticosteroid insensitivity in severe
ing TGF-β. Furthermore, major mast cells‘ asthma2,4.
