title: The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review.
abstract: Toll-like receptors (TLRs) constitute an important mechanism in the activation of innate immune cells including monocytes, macrophages and dendritic cells. Macrophage activation by TLRs is pivotal in the initiation of the rapid expression of pro-inflammatory cytokines TNF, IL-1β and IL-6 while promoting Th17 responses, all of which play critical roles in autoimmunity. Surprisingly, in inflammatory arthritis, activation of specific TLRs can not only induce but also inhibit cellular processes associated with bone destruction. The intercellular and intracellular orchestration of signals from different TLRs, their endogenous or microbial ligands and accessory molecules determine the activating or inhibitory responses. Herein, we review the TLR-mediated activation of innate immune cells in their activation and differentiation to osteoclasts and the capacity of these signals to contribute to bone destruction in arthritis. Detailed understanding of the opposing mechanisms of TLRs in the induction and suppression of cellular processes in arthritis may pave the way to develop novel therapies to treat autoimmunity.
authors: Biochemistry Research Institute of La Plata (INIBIOLP), Faculty of Medicine, National University of La Plata, La Plata, Argentina. Electronic address: mjimenez@med.unlp.edu.ar.
authors: Maximiliano Javier
authors: MJ
authors: Jiménez-Dalmaroni
authors: Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, 95616, USA.
authors: M Eric
authors: ME
authors: Gerswhin
authors: Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, 95616, USA; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, CA, 95817, USA. Electronic address: iannis@ucdavis.edu.
authors: Iannis E
authors: IE
authors: Adamopoulos
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000382:microbiology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D006801:Humans; D008024:Ligands; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D008024:Ligands; D051193:Toll-Like Receptors
keywords: Innate immunity; Osteoclasts; Rheumatoid arthritis; Toll-like receptors