New discoveries in CRMO: IL-1β, the neutrophil, and the microbiome implicated in disease pathogenesis in Pstpip2-deficient mice

被引:37
作者
Ferguson, Polly J. [1 ]
Laxer, Ronald M. [2 ,3 ]
机构
[1] Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA 52242 USA
[2] Hosp Sick Children, Div Rheumatol, Toronto, ON M5G 1X8, Canada
[3] Univ Toronto, Toronto, ON, Canada
基金
美国国家卫生研究院;
关键词
Chronic recurrent multifocal osteomyelitis; Pstpip2; Chronic non-bacterial osteomyelitis; Autoinflammatory; Interleukin-1; beta; RECURRENT MULTIFOCAL OSTEOMYELITIS; CONGENITAL DYSERYTHROPOIETIC ANEMIA; CHRONIC NONBACTERIAL OSTEOMYELITIS; AUTOINFLAMMATORY BONE DISORDERS; SATURATED FATTY-ACIDS; SAPHO-SYNDROME; HYPERTROPHIC OSTEODYSTROPHY; ASSOCIATION; PAMIDRONATE; MUTATION;
D O I
10.1007/s00281-015-0488-2
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Chronic non-bacterial osteomyelitis (CNO), chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome are autoinflammatory disorder(s) in which sterile osteomyelitis is frequently accompanied by inflammatory conditions of the joints, skin, or intestine. Patients with CRMO commonly have a personal or family history of psoriasis, inflammatory bowel disease, and inflammatory arthritis, suggesting shared disease pathogenesis. Work by our group and others has demonstrated that dysregulation of interleukin-1 (IL-1) signaling can drive sterile osteomyelitis in the two human monogenic forms of the disease. Recent work in the chronic multifocal osteomyelitis (cmo) mouse model demonstrates that the disease is IL-1-mediated, that neutrophils are critical effector cells and that both caspase-1 and caspase-8 play redundant roles in mediating the cleavage of pro-IL-1 beta into its biologically active form. Recent data in the cmo mouse demonstrate that dietary manipulation alters the cmo microbiome and can prevent the development of osteomyelitis. Further investigation is needed to determine the specific components of the diet that result in protection from disease and if this finding can be translated into a treatment for human CRMO.
引用
收藏
页码:407 / 412
页数:6
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