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Microbes & Immunity Big data and DNN-based DTI model in CHP

where CCL20 is expressed. This chemotactic response is healthy volunteers. Furthermore, CCL20 is a bifunctional
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crucial for the localization of Th17 cells to mucosal tissues peptide with both innate and adaptive immune properties,
and infection or inflammation sites. regulated by inflammatory mediators expressed by airway
Furthermore, Th2 cells are not only a subset of CD4 epithelia and increased in cystic fibrosis airway secretions.
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T-cells that are primarily involved in the immune response In summary, IL4 and IL13-induced CCL20 production
against extracellular parasites, such as helminths, and recruits CCR6 cells, potentially enhancing both Th2 and
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allergic reactions but also enhance the production of Th17 responses at inflammation sites. Compared to healthy
antibodies that are effective against extracellular parasites control lung tissues, hypersensitivity pneumonitis lung
and allergens. Naive CD4 T-cells differentiate into tissues exhibit increased expression of target genes IL4 and
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Th2 cells in response to specific cytokines and signals IL13. Through their involvement in immune cell recruitment,
from the immune environment. Target gene IL4 is the modulation of immune responses, promotion of fibrotic
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key cytokine driving this differentiation. Phosphorylated processes, and regulation of inflammatory mediators in the
STAT6 translocates to the nucleus to promote the CHP lung environment, IL4 and IL13 play important roles in
expression of Th2-related genes through TF GATA3, which immune response and pathogenesis in CHP.
leads to the expression of target genes of Th2-specific
cytokines, including IL4 and IL13. Cytokines IL-4 and 3.5. Selection of biomarkers as drug targets in CHP
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IL-13 induce the alternative activation of macrophages, for systematic drug discovery through a DNN-based
promoting an anti-inflammatory phenotype that supports DTI model
tissue repair and remodeling. Target genes IL4 and IL13 of After studying the pathogenetic mechanism of pulmonary
key cytokines also play a role in the pathogenesis of allergic cell fibrosis leading to CHP by observing abnormal apoptosis,
diseases, such as asthma. They contribute to airway immune response, and proliferation in downstream
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hyperresponsiveness, mucus production, and chronic cellular functions of the core signal pathways in Figure 4,
inflammation. Cytokines IL-4 and IL-13 can induce we identified important biomarkers of the CHP fibrosis
epithelial cells to undergo EMT, a process where epithelial mechanism as drug targets for treatment. Based on the
cells acquire mesenchymal, fibroblast-like properties, and fibrosis mechanism, CHP is characterized by proliferation
contribute to fibrosis. EMT is characterized by the loss of and apoptosis. According to the aforementioned core
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epithelial markers and the gain of mesenchymal markers, signal pathways and their downstream abnormal cellular
leading to increased migration, invasion, and extracellular functions in Figure 4, we selected important biomarkers
matrix production by these cells. In diseases such as related to abnormal inflammation, apoptosis, proliferation,
idiopathic pulmonary fibrosis and asthma, cytokines IL-4 angiogenesis, and cell cycle induced by external organic
and IL-13 contribute to the development of lung fibrosis by allergens. Therefore, we chose AKT1, CCL20, CDC23,
promoting the activation of fibroblasts and the production CXCL1, NF-κB, and TNF as important biomarkers, aiming
of extracellular matrix in the lungs. 83 to alleviate or exacerbate their expression levels, restoring
The right side of Figure 4 aims to characterize the them to normal inflammation, apoptosis, proliferation,
role of the chemotaxis CCL20/CCR6 and ERK signaling angiogenesis, and cell cycle levels. In addition, AKT1 and
pathways in CHP lung slice cells and non-CHP lung slice TNF play important roles in the MAPK/PI3K pathway.
cells. The expression and production of CCL20/CCR6 CCL20, CDC23, and CXCL1 are key regulators of cell
in CHP fibrosis samples obtained during surgery were migration, growth, and apoptosis in the Th17 pathway,
evaluated. In addition, colony formation, ERK signaling, whereas NF-κB is involved in cellular responses to various
and chemokine production were measured. It was found cellular stimuli. After identifying the important biomarkers
that CCL20 and CCR6 were highly expressed in most as drug targets, we considered their chemical properties.
samples from the recurrent group. Overall, these findings Based on DTI predictions using the DNN-based DTI
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suggest that CCR6 and CCL20 may play a role in lung model, we selected candidate molecular drugs for these
fibrosis, leading to proliferation and migration through drug targets (biomarkers).
autocrine or paracrine mechanisms. Disrupting the
CCL20/CCR6 interaction could be a promising strategy for The result of the DNN-based DTI model is a probability
treating fibrosis. CCL20 also has antibacterial properties value, where higher values correspond to more reliable
and is involved in lung innate immunity. The expression of interactions (docking) between the drug and the target.
CCL20 was significantly induced by TNF-α and suppressed The loss and accuracy during the training process are
by dexamethasone. Studies have shown that the abundance recorded in Figures 6 and 7, respectively.
of CCL20 in bronchoalveolar lavage fluid from cystic Predictions are made based on high-probability
fibrosis patients is nearly 90 times higher than that from biomarkers to find suitable candidate molecular drugs.

Volume 2 Issue 2 (2025) 99 doi: 10.36922/mi.4620