The critical role of toll-like receptors — From microbial recognition to autoimmunity: A comprehensive review

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• 作者：Maximiliano Javier Jimé ; nez-Dalmaroni^a ; ^{mjimenez@med.unlp.edu.ar" class="auth_mail" title="E-mail the corresponding author} ; M. Eric Gerswhin^b ; Iannis E. Adamopoulos^b ; ^c ; ^{iannis@ucdavis.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TLRs ; Toll-like receptors ; RA ; Rheumatoid arthritis ; PRRs ; Pattern Recognition Receptors ; ED ; Ectodomain ; NFκB ; nuclear factor kappa-light-chain-enhancer of activated B cells ; PAMPs ; Pathogen Associated Molecular Patterns ; HMGB-1 ; high mobility group box-1 ; CD14 ; cluster of differentiation 14 ; CD36 ; cluster of differentiation 36 ; UNC93B1 ; unc-93 homolog B1 ; TRAF-6 ; tumor necrosis-factor-receptor-associated-factor 6 ; oxLDL ; oxidized LDL ; MyD88 ; myeloid differentiation factor 88 ; TRIF ; toll/interf
• 刊名：Autoimmunity Reviews
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：15
• 期：1
• 页码：1-8
• 全文大小：1083 K

文摘

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.