Th17 Pathway-Mediated Immunopathogenesis of Schizophrenia: Mechanisms and Implications

被引:85
作者
Debnath, Monojit [1 ]
Berk, Michael [2 ,3 ]
机构
[1] Natl Inst Mental Hlth & Neurosci, Dept Human Genet, Bangalore 560029, Karnataka, India
[2] Deakin Univ, Sch Med, IMPACT Strateg Res Ctr, Geelong, Vic 3217, Australia
[3] Univ Melbourne, Dept Psychiat, Florey Inst Neurosci & Mental Hlth, Orygen Youth Hlth Res Ctr, Parkville, Vic 3052, Australia
基金
英国医学研究理事会;
关键词
Th17; cells; IL-17; cytokine; inflammation; neuroprogression; schizophrenia; pathogenesis; etiology; fetal; MATERNAL IMMUNE STIMULATION; REGULATORY T-CELLS; BACTERIAL TRANSLOCATION; INCREASED EXPRESSION; AUTOIMMUNE-DISEASES; THERAPEUTIC TARGET; ADAPTIVE IMMUNITY; GUT MICROBIOTA; MESSENGER-RNA; DRUG-NAIVE;
D O I
10.1093/schbul/sbu049
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Schizophrenia is a highly complex and severe neuropsychiatric disorder with an unknown etiopathology. Evidence for a dysregulated immune system in both the risk for and progression of schizophrenia has recently been overwhelming. Importantly, chronic low-grade inflammation both in the periphery and central nervous system has been shown to contribute predominantly to the pathogenesis of schizophrenia in a subset of individuals. Inflammation in the central nervous system is mediated by a range of proinflammatory cytokines, resident immune cells such as microglia, and brain infiltrating peripheral immunocompetent cells, such as T lymphocytes. Recently, Th17 cells, a subset of T helper cells have emerged as crucial players in mucosal defense against infections. It is linked to atopic, inflammatory, and autoimmune disorders. The risk factors/mechanisms leading to low-grade inflammation in schizophrenia are diverse and include infectious agents, stress, trauma, environmental toxins, genetic vulnerability, physical inactivity, obesity, poor diet, and sleep disruption. Herein, we propose that fetal programming of cellular immune components driven by intrauterine adversity can lead to the generation of long-lasting effector/memory Th17 cells. Th17 cells can disrupt the blood-brain barrier, infiltrate the central nervous system, and, along with other cytokines and microglia, lead to neuroprogression through neuroinflammation in schizophrenia.
引用
收藏
页码:1412 / 1421
页数:10
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