title: Toll-like receptor signaling mechanisms involved in dendritic cell activation: potential therapeutic control of T cell polarization.
abstract: Dendritic cells (DCs) represent a bridge between innate and adaptive immunity, being the maturation process dependent on the binding of pathogen-associated molecular patterns (PAMPs) to Toll-Like Receptors (TLRs) expressed on their surface. TLRs associated to adaptor proteins, following binding to PAMPs, are able to skew specific immune responses towards the T helper (h)(1)- or the Th(2)-type according to the antigenic stimulation involved. Of note, other receptors different from TLRs are expressed on DCs which are also able to recognize PAMPs. Among them, one should mention the DC-specific ICAM-3-grabbing nonintegrin, the mannose receptor, Dectin-1 (the major beta-glucan receptor) and NOD2. Finally, the possibility to interfere therapeutically with the TLR-dependent and -independent signaling pathways in DCs is reviewed. According to current literature, DC activation, their antigen uptake capacity and migration can be enhanced with different experimental procedures whose use in humans is still under evaluation. However, just recently a probiotic cocktail VSL3, successfully used in patients with pouchitis, seems to act on DCs, promoting abundant release of Interleukin-10 in the gut. These novel therapeutic strategies based on the modulation of the signaling pathways in DCs seem to be encouraging for the treatment of inflammatory and autoimmune diseases.
authors.affiliation: National Institute for Digestive Diseases, Castellana Grotte, Bari, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Amati
authors.forename: Maria
authors.initials: M
authors.lastname: Pepe
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Passeri
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Mastronardi
authors.forename: Emilio
authors.initials: E
authors.lastname: Jirillo
authors.forename: Vito
authors.initials: V
authors.lastname: Covelli
mesh_terms: D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D051193:Toll-Like Receptors