Onset and persistence of the allergic inflammation: a molecular explanation?
Allergic respiratory inflammation in target organs does not occur in any atopic (genetically susceptible) subject, since other not fully characterized factors can influence the subsequent development of overt clinical disease. Here are presented some recent developments in experimental animal and human research that can offer a new "non-classical" interpretation about the way by which allergens are recognized and allergic inflammation persists. These aspects of the immunopathogenesis of allergic diseases can now be viewed as organ-specific pathways, acting independently from other peripheral lymphoid organs. This is a consequence of new knowledge about the function of, and molecular interactions by, intraepithelial gammadelta T cells and CD1+ dendritic cells. The allergic subject, unlike the normal one, is equipped at the mucosal surface by particular T cell and antigen-presenting cell (APC) subsets that enable them to recognize undenatured proteic and non-proteic (glycolipidic) external structures of aerodispersed particles, presented in the context of CD1 molecules. Once initiated, the mucosal allergic reaction cannot be turned off in atopic individuals because CD4+ allergen-specific T cells lack surface Fas receptor. This defect, that impairs the so-called activation-induced programmed cell death (determined by Fas/FasL interaction), is caused by the local Th2-type cytokine milieu.
Spinozzi
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Department of Clinical and Experimental Medicine, University of Perugia, Policlinico Monteluce, Italy.
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D053222:Fas Ligand Protein; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor