The Critical Role of Toll-like Receptors--From Microbial Recognition to Autoimmunity: A Comprehensive Review

Overview

Journal Autoimmun Rev

Publisher Elsevier

Specialty Allergy & Immunology

Date 2015 Aug 25

PMID 26299984

Citations 114

Authors

Maximiliano Javier Jimenez-Dalmaroni

M Eric Gerswhin

Iannis E Adamopoulos

Affiliations

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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.

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