loading...| Preferred Name |
Atopic Dermatitis |
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| Synonyms |
PMID: 19494826 PathwayType: signaling Organ: skin CellType: T-cell CellType: corneocyte PMID: 20081870 Description: Atopic dermatitis (AD) is a chronic skin disorder that involves scaly and itchy rashes. Pathway is built manually using published studies. Notes: Headnote: Atopic dermatitis (AD) is a chronic skin disorder characterized by scaly and itchy rashes. It typically involves a skin reaction similar to an allergy, which leads to an ongoing swelling and redness. AD is associated with the impaired skin barrier function and IgE-mediated sensitization to food and environmental allergens. Signaling description: Skin penetration barrier is located in the lower part of the stratum corneum (SC). Structural integrity of the SC is maintained by the presence of modified desmosomes known as corneodesmosomes, which bind the corneocytes together. Corneodesmosomes are formed by members of the cadherin family of extracellular transmembrane glycoproteins including desmoglein (DSG) and desmocollin (DSC). Within the corneocytes, DSG and DSC are linked to keratin filaments through corneodesmosomal plaque proteins including plakoglobin (JUP), desmoplakin (DSP), and plakophilin (PKP). DSG and DSC migrate from the corneocyte envelope into the lipid lamellae sandwiched between the corneocytes and bind to the corneodesmosomal plaque proteins on adjacent cells. Also, filaggrin (FLG) is an epithelial cell protein, which is extensively deaminated through the actions of the peptidyl deiminase (PADI1) enzyme. It is subsequently degraded into small peptides and then into free amino acids, which are then catabolized into the components of natural moisturizing factor (NMF) including lactic acid, sodium pyrrolidone carboxylic acid, urocanate, and urea. The NMF is essential for the retention of water within the corneocytes and results in their optimal hydration and swelling. The human kallikrein (KLK)-related peptidases such as SC chymotryptic enzyme (KLK7) and SC tryptic enzyme (KLK5) are key proteases involved in desquamation. Their increased expression can lead to impaired epidermal barrier function in AD. KLK7, with chymotrypsin-like activity, has been shown to hydrolyze corneodesmosin (CDSN) and desmocollin 1 (DSC1), whereas KLK5 can cleave desmoglein 1 (DSG1) with its trypsin-like activity. Enzymatically active KLK14, also exhibiting trypsin-like activity is present in the SC, where it cleaves DSG1. In addition, SPINK5 is a potent inhibitor of both KLK5 and KLK7, and thus, is critical for epidermal barrier function. As the pH becomes more acidic, the inhibitory potential of SPINK5 is reduced. The inhibition by SPINK5 in the superficial layers of the SC is sufficiently reduced to support localized desquamation. Outcome effects: Following contact with an antigen e.g. Staphylococcus aureus, during the elicitation phase cutaneous professional antigen presenting cells migrate to regional lymph nodes, where they present the processed peptides to naive T-cells. In the presence of IL4, naive T-lymphocytes differentiate toward the Th2 phenotype and induce class switching of B- lymphocytes to IgE production. Circulating IgE binds to high affinity IgE receptors on tissue resident mast cells. A second exposure to the antigen causes cell reactivation, mast cell degranulation, and release of inflammatory molecules such as histamine, IL8, and IL13 which causes a Th2-lymphocyte influx into the skin. However, with the infiltration of eosinophils and macrophages in chronic AD, there is a rise in IL12 expression and a switch to Th1 cellular responses. Acute skin lesions of patients with AD have increased amounts of cells positive for IL4, IL5, and IL13 mRNA compared to normal or uninvolved skin. In contrast, there are few IFNG or IL12 mRNA expressing cells in acute skin lesions of patients with AD. Lastly, recent evidence suggests a possible role for IL33/IL1RL1 pathway in epithelial integrity, allergic immune responses, inflammation, autoimmunity, and fibrosis. IL33-dependent activation of IL1RL1 signaling leads to the activation of MAPK and NF-kB signaling which ultimately have roles in the pathogenesis of AD. The mature form of IL33 is released into the cytoplasm and thus stimulates T-cells, mast cells, or keratino PMID: 22499037 CellType: mast cell NodeType: Pathway Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-7bbbbfa5-94a0-40de-807f-4d29a0f39a26 Tissue: epidermis Pathway_Author: V. Sobolev ORCID:0000-0003-4779-156X Organ_System: integumentary system PMID: 21249468 PMID: 22561834 Source: Diseases |
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| ID |
urn:agi-pathway:uuid-7bbbbfa5-94a0-40de-807f-4d29a0f39a26 |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PMID: 19494826 PathwayType: signaling Organ: skin CellType: T-cell CellType: corneocyte PMID: 20081870 Description: Atopic dermatitis (AD) is a chronic skin disorder that involves scaly and itchy rashes. Pathway is built manually using published studies. Notes: Headnote: Atopic dermatitis (AD) is a chronic skin disorder characterized by scaly and itchy rashes. It typically involves a skin reaction similar to an allergy, which leads to an ongoing swelling and redness. AD is associated with the impaired skin barrier function and IgE-mediated sensitization to food and environmental allergens. Signaling description: Skin penetration barrier is located in the lower part of the stratum corneum (SC). Structural integrity of the SC is maintained by the presence of modified desmosomes known as corneodesmosomes, which bind the corneocytes together. Corneodesmosomes are formed by members of the cadherin family of extracellular transmembrane glycoproteins including desmoglein (DSG) and desmocollin (DSC). Within the corneocytes, DSG and DSC are linked to keratin filaments through corneodesmosomal plaque proteins including plakoglobin (JUP), desmoplakin (DSP), and plakophilin (PKP). DSG and DSC migrate from the corneocyte envelope into the lipid lamellae sandwiched between the corneocytes and bind to the corneodesmosomal plaque proteins on adjacent cells. Also, filaggrin (FLG) is an epithelial cell protein, which is extensively deaminated through the actions of the peptidyl deiminase (PADI1) enzyme. It is subsequently degraded into small peptides and then into free amino acids, which are then catabolized into the components of natural moisturizing factor (NMF) including lactic acid, sodium pyrrolidone carboxylic acid, urocanate, and urea. The NMF is essential for the retention of water within the corneocytes and results in their optimal hydration and swelling. The human kallikrein (KLK)-related peptidases such as SC chymotryptic enzyme (KLK7) and SC tryptic enzyme (KLK5) are key proteases involved in desquamation. Their increased expression can lead to impaired epidermal barrier function in AD. KLK7, with chymotrypsin-like activity, has been shown to hydrolyze corneodesmosin (CDSN) and desmocollin 1 (DSC1), whereas KLK5 can cleave desmoglein 1 (DSG1) with its trypsin-like activity. Enzymatically active KLK14, also exhibiting trypsin-like activity is present in the SC, where it cleaves DSG1. In addition, SPINK5 is a potent inhibitor of both KLK5 and KLK7, and thus, is critical for epidermal barrier function. As the pH becomes more acidic, the inhibitory potential of SPINK5 is reduced. The inhibition by SPINK5 in the superficial layers of the SC is sufficiently reduced to support localized desquamation. Outcome effects: Following contact with an antigen e.g. Staphylococcus aureus, during the elicitation phase cutaneous professional antigen presenting cells migrate to regional lymph nodes, where they present the processed peptides to naive T-cells. In the presence of IL4, naive T-lymphocytes differentiate toward the Th2 phenotype and induce class switching of B- lymphocytes to IgE production. Circulating IgE binds to high affinity IgE receptors on tissue resident mast cells. A second exposure to the antigen causes cell reactivation, mast cell degranulation, and release of inflammatory molecules such as histamine, IL8, and IL13 which causes a Th2-lymphocyte influx into the skin. However, with the infiltration of eosinophils and macrophages in chronic AD, there is a rise in IL12 expression and a switch to Th1 cellular responses. Acute skin lesions of patients with AD have increased amounts of cells positive for IL4, IL5, and IL13 mRNA compared to normal or uninvolved skin. In contrast, there are few IFNG or IL12 mRNA expressing cells in acute skin lesions of patients with AD. Lastly, recent evidence suggests a possible role for IL33/IL1RL1 pathway in epithelial integrity, allergic immune responses, inflammation, autoimmunity, and fibrosis. IL33-dependent activation of IL1RL1 signaling leads to the activation of MAPK and NF-kB signaling which ultimately have roles in the pathogenesis of AD. The mature form of IL33 is released into the cytoplasm and thus stimulates T-cells, mast cells, or keratino PMID: 22499037 CellType: mast cell NodeType: Pathway Tissue: epidermis Pathway_Author: V. Sobolev ORCID:0000-0003-4779-156X Organ_System: integumentary system PMID: 21249468 PMID: 22561834 Source: Diseases |
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| id |
urn:agi-pathway:uuid-7bbbbfa5-94a0-40de-807f-4d29a0f39a26 |
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| label |
Atopic Dermatitis |
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| notation |
uuid-7bbbbfa5-94a0-40de-807f-4d29a0f39a26 |
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| prefLabel |
Atopic Dermatitis |
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| treeView |
urn:agi-folder:a urn:agi-folder:atopic_dermatitis urn:agi-folder:epidermis urn:agi-folder:integumentary_system |
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| subClassOf |
urn:agi-folder:a urn:agi-folder:atopic_dermatitis urn:agi-folder:epidermis urn:agi-folder:integumentary_system |