Therapy directed against thymic stromal lymphopoietin.
Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine and has been shown to be one of the factors released by epithelial cells following allergen contact with an important role instructing dendritic cells (DCs) to induce a T-helper type 2 (Th2) response. These TSLP-DC stimulate CD4(+) T cells to induce a proallergic cytokine profile, suggesting TSLP plays a crucial role in the initiation of the allergic cascade. Recently, evidence has also accumulated that TSLP could play a role in enhancement of the effector stages of the allergic response, with TSLP in synergy with IL-1 and tumor necrosis factor (TNF)-alpha shown to amplify cytokine secretion from mast cells. Also, the clinical relevance of TSLP has been demonstrated by both high levels of TSLP in skin biopsies from lesional atopic dermatitis patients and also increased expression of TSLP in asthmatic airway epithelial cells which correlated with reduced lung function. These studies suggest a critical role for TSLP as a driving factor in the emerging concept of tissue-specific control of immunity with TSLP secretion at the epithelial-DC interface acting as an initial factor in the proallergic cascade.
Edwards
Matthew J
MJ
Respiratory Disease Area, Novartis Institute of Biomedical Research, Horsham, UK. matt.edwards@novartis.com
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects*; D000094632:Thymic Stromal Lymphopoietin
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin