젊은 사람들이 나이든 사람들에 비해 인간광우병에 민감한 이유를 밝히려는 연구결과 중 2009년 10월 영국 에딘버러대학교의 로슬린연구소의 Neil Mabbott 박사팀이 [면역학회지(The Journal of Immunology)]에 발표한 논문의 요약문입니다.
변형 프리온은 중추신경계로 퍼지기 전에 비장, 림파구, 편도 등 면역계의 일부인 림프조직에 축적되는데, Neil Mabbott를 비롯한 로슬린 연구소의 학자들은 프리온은 필수불가결하게 면역계의 특별한 세포인 소포성 수지상 세포 (follicular dendritic cells)를 “납치(hijack)”하는 것을 확인했습니다.(변형 프리온 단백질이 소포성 수지상 세포와 반드시 결합하여 그 세포에서 축적되고 복제됩니다)
그러나 나이 든 쥐에서는 소포성 수지상 세포가 손상된(감소된) 것이 확인됐습니다.
광우병과 소포성 수지상 세포 (follicular dendritic cells)의 연관성은 예전에 [네이처]에도 발표된 바가 있습니다.
논문의 영문 요약문과 출처는 아래와 같습니다.
The Effects of Host Age on Follicular Dendritic Cell Status Dramatically Impair Scrapie Agent Neuroinvasion in Aged Mice1
Karen L. Brown,2* Gwennaelle J. Wathne,* Jill Sales,
Moira E. Bruce,* and Neil A. Mabbott2* *The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Roslin, United Kingdom; and Biomathematics & Statistics Scotland, Edinburgh, United Kingdom
출처 : Published online September 28, 2009
The Journal of Immunology, 2009, 183, 5199 -5207
http://www.jimmunol.org/cgi/
doi:10.4049/jimmunol.0802695
Following peripheral exposure, many transmissible spongiform encephalopathy (TSE) agents accumulate first in lymphoid tissues before spreading to the CNS (termed neuroinvasion) where they cause neurodegeneration. Early TSE agent accumulation upon follicular dendritic cells (FDCs) in lymphoid follicles appears critical for efficient neuroinvasion. Most clinical cases of variant Creutzfeldt-Jakob disease have occurred in young adults, although the reasons behind this apparent age-related susceptibility are uncertain. Host age has a significant influence on immune function. As FDC status and immune complex trapping is reduced in aged mice (600 days old), we hypothesized that this aging-related decline in FDC function might impair TSE pathogenesis. We show that coincident with the effects of host age on FDC status, the early TSE agent accumulation in the spleens of aged mice was significantly impaired. Furthermore, following peripheral exposure, none of the aged mice developed clinical TSE disease during their lifespans, although most mice displayed histopathological signs of TSE disease in their brains. Our data imply that the reduced status of FDCs in aged mice significantly impairs the early TSE agent accumulation in lymphoid tissues and subsequent neuroinvasion. Furthermore, the inefficient neuroinvasion in aged individuals may lead to significant levels of subclinical TSE disease in the population.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by funding from the European Commission, UK Biotechnology and Biological Sciences Research Council, and the Medical Research Council.
2 Address correspondence and reprint requests to Dr. Karen L. Brown and Dr. Neil A. Mabbott, The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Roslin, Midlothian EH25 9PS, U.K. E-mail: karen.brown@roslin.ed.ac.uk and neil.mabbott@roslin.ed.ac.uk
3 Abbreviations used in this paper: TSE, transmissible spongiform encephalopathy; FDC, follicular dendritic cell; PrP, prion protein; vCJD, variant Creutzfeldt-Jakob disease; BSE, bovine spongiform encephalopathy; CR, complement receptor; i.c., intracerebral; TH, tyrosine hydroxylase; PK, proteinase K.
4 The online version of this article contains supplemental material.
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Dr Neil Mabbott
Identification of critical cells and molecules involved in the delivery of TSE agents from the site of infection to the brain.
출처 : http://www.roslin.ac.uk/research/people.php/Neil.Mabbott
Contact Details
Dr Neil Mabbott
Group Leader
Neuropathogenesis Division
The Roslin Institute and R(D)SVS, University of Edinburgh
Roslin Biocentre
Roslin Institute
Midlothian
EH25 9PS
Tel: 0131 527 4200
Fax: 0131 440 0434
e-mail: neil.mabbott@roslin.ed.ac.uk
