IL-17A Signaling in Airway Cells
IL-17A (also referred to as IL-17) is a member of the family of IL-17 ligands which also includes IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. It is mainly produced by a subset of T cells called TH17. TH17 cells are driven to differentiate by TGF-β, IL-1 and IL-6, while IL-23 is required to expand and stabilize the cell population. IL-17A has also been detected in other cells such as neutrophils and macrophages. While IL-17A is linked to the pathogenesis of diverse autoimmune and inflammatory diseases, it also plays an essential role in host defense against extracellular bacteria and fungi...
Pathway Summary
IL-17A (also referred to as IL-17) is a member of the family of IL-17 ligands which also includes IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. It is mainly produced by a subset of T cells called TH17. TH17 cells are driven to differentiate by TGF-β, IL-1 and IL-6, while IL-23 is required to expand and stabilize the cell population. IL-17A has also been detected in other cells such as neutrophils and macrophages. While IL-17A is linked to the pathogenesis of diverse autoimmune and inflammatory diseases, it also plays an essential role in host defense against extracellular bacteria and fungi.The presence of IL-17A in the airway lumen is a hallmark of several inflammatory lung disorders, such as chronic obstructive pulmonary disease (COPD) and asthma. Different signaling pathways mediate IL-17A induced gene expression in airway cells such as epithelial and smooth muscle cells. In vivo, IL-17A forms homodimers, binds to and activates a heterodimeric receptor complex consisting of IL-17RC and IL-17RA subunits. The IL-17R complex does not possess intrinsic enzymatic activity but induces signaling via recruitment of signaling intermediates. Airway epithelial cells utilize NF-κB and PI3K/AKT signaling pathways. The PI3K/AKT pathway involves the phosphorylation and activation of JAK kinases upstream of PI3K, while the NF-κB pathway requires ACT-1, a SEFIR-domain containing protein and TRAF-6, an E3 ubiquitin ligase. Together they activate TRAF-1 leading eventually to the activation and nuclear translocation of NF-κB. NF-κB induces transcription of various genes that regulate inflammation, chemotaxis, mucous hypersecretion and antimicrobial activity.Airway smooth muscle cells are key determinants of asthma due to their ability to contract in response to inflammatory cell products. IL-17A has been shown to activate MAPK and JAK/STAT signaling in these cells. MAPKs (ERK, JNK and p38 MAPK) and JAKs are phosphorylated in response to IL-17A, resulting in the induction of Eotaxin (CCL11). Eotaxin is a chemokine required for eosinophil recruitment and promotion of airway inflammation in asthma. Thus, IL-17A plays a key part in airway inflammatory diseases.
IL-17A Signaling in Airway Cells Genes list
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AKT1AKT serine/threonine kinase 1 AKT2AKT serine/threonine kinase 2 AKT3AKT serine/threonine kinase 3 CCL11C-C motif chemokine ligand 11 CCL20C-C motif chemokine ligand 20 CHUKcomponent of inhibitor of nuclear factor kappa B kinase complex CXCL1C-X-C motif chemokine ligand 1 CXCL2C-X-C motif chemokine ligand 2 CXCL3C-X-C motif chemokine ligand 3 CXCL5C-X-C motif chemokine ligand 5 CXCL6C-X-C motif chemokine ligand 6 DEFB4Adefensin beta 4A GSK3Bglycogen synthase kinase 3 beta IKBKBinhibitor of nuclear factor kappa B kinase subunit beta IKBKEinhibitor of nuclear factor kappa B kinase subunit epsilon IKBKGinhibitor of nuclear factor kappa B kinase regulatory subunit gamma IL17Ainterleukin 17A IL17RAinterleukin 17 receptor A IL17RBinterleukin 17 receptor B IL17RCinterleukin 17 receptor C IL19interleukin 19 IL6interleukin 6 JAK1Janus kinase 1 JAK2Janus kinase 2 JAK3Janus kinase 3 MAP2K1mitogen-activated protein kinase kinase 1 MAP2K2mitogen-activated protein kinase kinase 2 MAP2K4mitogen-activated protein kinase kinase 4 MAP3K7mitogen-activated protein kinase kinase kinase 7 MAPK1mitogen-activated protein kinase 1 MAPK10mitogen-activated protein kinase 10 MAPK11mitogen-activated protein kinase 11 MAPK12mitogen-activated protein kinase 12 MAPK13mitogen-activated protein kinase 13 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 MAPK8mitogen-activated protein kinase 8 MAPK9mitogen-activated protein kinase 9 MUC5ACmucin 5AC, oligomeric mucus/gel-forming MUC5Bmucin 5B, oligomeric mucus/gel-forming NFKB1nuclear factor kappa B subunit 1 NFKB2nuclear factor kappa B subunit 2 NFKBIANFKB inhibitor alpha NFKBIBNFKB inhibitor beta NFKBIDNFKB inhibitor delta NFKBIENFKB inhibitor epsilon PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PTENphosphatase and tensin homolog RELREL proto-oncogene, NF-kB subunit RELARELA proto-oncogene, NF-kB subunit RELBRELB proto-oncogene, NF-kB subunit STAT3signal transducer and activator of transcription 3 TRAF3IP2TRAF3 interacting protein 2 TRAF6TNF receptor associated factor 6 TYK2tyrosine kinase 2
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