Imperial College London
Alternate

ProfessorMatthewPickering

Faculty of Medicine, Department of Immunology and Inflammation

Centre Director, Professor of Rheumatology
 
 
 
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Contact

 

matthew.pickering Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N12Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kane:2017:10.4049/jimmunol.1701100,
author = {Kane, SJ and Farley, TK and Gordon, EO and Estep, J and Bender, HR and Moreno, JA and Bartz, J and Telling, GC and Pickering, MC and Zabel, MD},
doi = {10.4049/jimmunol.1701100},
journal = {Journal of Immunology},
pages = {3821--3827},
title = {Complement regulatory protein factor H is a soluble prion receptor that potentiates peripheral prion pathogenesis},
url = {http://dx.doi.org/10.4049/jimmunol.1701100},
volume = {199},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Several complement proteins exacerbate prion disease, including C3, C1q, and CD21/35. These proteins of the complement cascade likely increase uptake, trafficking, and retention of prions in the lymphoreticular system, hallmark sites of early prion propagation. Complement regulatory protein factor H (fH) binds modified host proteins and lipids to prevent C3b deposition and, thus, autoimmune cell lysis. Previous reports show that fH binds various conformations of the cellular prion protein, leading us to question the role of fH in prion disease. In this article, we report that transgenic mice lacking Cfh alleles exhibit delayed peripheral prion accumulation, replication, and pathogenesis and onset of terminal disease in a gene-dose manner. We also report a biophysical interaction between purified fH and prion rods enriched from prion-diseased brain. fH also influences prion deposition in brains of infected mice. We conclude from these data and previous findings that the interplay between complement and prions likely involves a complex balance of prion sequestration and destruction via local tissue macrophages, prion trafficking by B and dendritic cells within the lymphoreticular system, intranodal prion replication by B and follicular dendritic cells, and potential prion strain selection by CD21/35 and fH. These findings reveal a novel role for complement-regulatory proteins in prion disease.
AU  - Kane,SJ
AU  - Farley,TK
AU  - Gordon,EO
AU  - Estep,J
AU  - Bender,HR
AU  - Moreno,JA
AU  - Bartz,J
AU  - Telling,GC
AU  - Pickering,MC
AU  - Zabel,MD
DO  - 10.4049/jimmunol.1701100
EP  - 3827
PY  - 2017///
SN  - 1550-6606
SP  - 3821
TI  - Complement regulatory protein factor H is a soluble prion receptor that potentiates peripheral prion pathogenesis
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.1701100
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000415967800013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
VL  - 199
ER  -
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