Figure Legends
Figure 1: Immune responses and mechanisms of asthma. The
external environment can impair the epithelial barrier. The disrupted
barrier allows the penetration of the substances through the tissues
where they encounter the antigen presenting cells. Additionally,
submucosal DCs can gain access to outside the epithelium by screening
with their dendrites. Activated or damaged epithelial cells stimulate
DCs through their secreted cytokines: TSLP, IL-25, IL-33. After
capturing the antigen DCs migrate through the lymphatics to regional
lymph nodes and prime the naïve T cells. The differentiation into Th2
cells is driven mainly by IL-4. Mature DCs and TSLP, IL-25 and IL33
directly or indirectly stimulate tissue-resident ILC2‘s. Th2 cells and
ILC2 secrete mainly IL-5, IL-9 and IL-13 but also small amounts of IL-4.
While IL-5 stimulates eosinophils, IL-9 and IL-13 induce mucus
production and activation of epithelium and mast cells. IL-4, IL-13 are
involved in the opening the epithelial barrier, activation of the
endothelium and migration of Th2 cells, ILC2 and eosinophils and IgE
class switching in B cells. After the sensitization of mast cells due to
the binding of specific IgE to FcεR, upon crosslinking of IgE, they get
activated and release histamine, tryptase, prostaglandins, leukotrienes
and cytokines, which leads to smooth muscle contraction, mucus
production and increased vascular permeability. While Th2 resident
memory cells proliferate close to airways, circulating memory Th2 cells
traffic into the lung parenchyma and initiate a perivascular
inflammation with eosinophil and CD4+ T cell
recruitment, further augmenting type 2 cytokine production within the
lung. Eosinophils cross talk with the resident tissue cells through
their secreted leukotrienes and specific proteins such as MBP and EPO.
Furthermore, several substances, such as bacteria and mold-derived
molecules in allergens can induce Th17 and neutrophil recruitment.
Immune regulation mechanisms prevent type1, type 2 and type 17 response
through Breg and Treg cells and particularly IL-10, IL-35 and TGF- β. In
addition, IgG4 has a blocking antibody function for IgE binding to
allergens. Several drugs target type 2 cytokines or their receptors
signalling: the IL-5 pathway (benralizumab, mepolizumab, reslizumab),
the IL-4 and IL-13 pathway (dupilumab) and IgE pathway (omalizumab).
Breg, B regulatory cell; Circ, circulating; DC, dendritic cell; EOS,
eosinophil; EPO, eosinophil peroxidase; GM-CSF, granulocyte-macrophage
colony-stimulating factor; HDM, house dust mite; IFN-γ, interferon-γ;
Ig, immunoglobulin; IL, interleukin; IL-4Rα, interleukin 4 receptor
alfa; ILC2, innate lymphoid cell 2; LT, leukotriene; MBP, major basic
protein; MC, mast cell; NEU, neutrophil; PGD2, Prostaglandin D2; PM,
particulate matter; TGF-β, tumor growth factor- β; Th2 Trm, T helper 2
tissue resident memory; TNF, tumor necrosis factor;Treg, t regulatory
cell; TSLP, thymic stromal lymphopoietin.