Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive polyarthritis. Beyond joint pathology, RA is associated with neuropsychiatric comorbidity including depression, anxiety, and an increased risk to develop neurodegenerative diseases in later life. Studies investigating the central nervous system (CNS) in preclinical models of RA have leveraged the understanding of the intimate crosstalk between peripheral and central immune responses. This mini review summarizes the current knowledge of CNS comorbidity in RA patients and known underlying cellular mechanisms. We focus on the differential regulation of CNS myeloid and glial cells in different mouse models of RA reflecting different patterns of peripheral immune activation. Moreover, we address CNS responses to anti-inflammatory treatment in human RA patients and mice. Finally, to illustrate the bidirectional communication between the CNS and chronic peripheral inflammation, we present the current knowledge about the impact of the CNS on arthritis. A comprehensive understanding of the crosstalk between the CNS and chronic peripheral inflammation will help to identify RA patients at risk of developing CNS comorbidity, setting the path for future therapeutic approaches in both RA and neuropsychiatric diseases.
Highlights
The central nervous system (CNS) has long been considered to be protected from circulatory inflammatory signals by the blood-brain barrier (BBB)
An intimate crosstalk between chronic peripheral inflammation and the CNS is evidenced by a plethora of neurological and psychiatric sequelae associated with chronic inflammatory diseases like rheumatoid arthritis (RA)
Almost 40% of RA patients experience chronic pain, which is further linked to depression and anxiety [9]
Summary
The central nervous system (CNS) has long been considered to be protected from circulatory inflammatory signals by the blood-brain barrier (BBB). Direct stimulation of splenic nerve terminals by ultrasound altered gene expression profiles of B and T cells and alleviated arthritis in the K/BxN serum transfer model, which is mediated by antibodies against glucose-6-phosphate isomerase [79] To date, it is hardly understood, how this modulation of chronic peripheral inflammation via the autonomic nervous system is orchestrated by central brain regions. Post-stroke immunosuppression alleviated K/BxN serum transfer-induced arthritis in mice during early disease stages [83] These data suggest that certain CNS regions may on the one hand be a target, but on the other hand a modulator of chronic peripheral inflammation in the context of RA. All authors contributed to the article and approved the submitted version
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