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Regulation of microglia activation and deactivation by nuclear receptors
Author(s) -
Saijo Kaoru,
Crotti Andrea,
Glass Christopher K.
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22423
Subject(s) - microglia , biology , innate immune system , inflammasome , pattern recognition receptor , receptor , neuroscience , microbiology and biotechnology , neuroinflammation , proinflammatory cytokine , immune system , immunology , inflammation , genetics
Microglia cells function as sentinels for innate immunity in the central nervous system (CNS). To perform this function, microglia express a diverse set of pattern recognition receptors (PRRs) for pathogen‐associated molecular patterns (PAMPs) that include Toll‐like receptors (TLRs) and inflammasomes. Several members of the TLR and inflammasome family also recognize endogenously derived molecules that are generated as a consequence of tissue injury or other pathological processes. Recognition of PAMPs or endogenous ligands by PRRs in microglia induces the robust activation of innate immune responses leading to the production of proinflammatory mediators and the activation of adaptive immunity. Activation of microglia is essential for clearance of infection and repair of tissue injury. However, uncontrolled inflammatory responses of microglia are also thought to contribute to the severity of many neurodegenerative diseases. Thus, activation of microglia must be properly and tightly regulated to maintain normal tissue homeostasis. Several mechanisms have been identified that appear to function in the active maintenance of quiescence under normal conditions and/or re‐establish this state following resolution of infection or injury. These mechanisms involve communication with neurons and other glia through secreted molecules or surface expressing receptors as well as actions of members of the nuclear receptor (NR) superfamily of transcription factors. Here, we review recent advances in our understanding of the regulation of microglia activation and deactivation with a focus on counter‐regulation of microglia activation by nuclear receptors. © 2012 Wiley Periodicals, Inc.