Imperial College London
Alternate

ProfessorMarinaBotto

Faculty of Medicine, Department of Immunology and Inflammation

Head of Department, Director of Bioservices
 
 
 
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Contact

 

+44 (0)20 3313 2316m.botto Website

 
 
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Assistant

 

Miss Claudia Rocchi +44 (0)20 3313 2315

 
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Location

 

9N10Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Clarke:2015:10.1136/annrheumdis-2013-204343,
author = {Clarke, AJ and Ellinghaus, U and Cortini, A and Stranks, A and Simon, AK and Botto, M and Vyse, TJ},
doi = {10.1136/annrheumdis-2013-204343},
journal = {Annals of the Rheumatic Diseases},
pages = {912--920},
title = {Autophagy is activated in systemic lupus erythematosus and required for plasmablast development},
url = {http://dx.doi.org/10.1136/annrheumdis-2013-204343},
volume = {74},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background Autophagy has emerged as a critical homeostatic mechanism in T lymphocytes, influencing proliferation and differentiation. Autophagy in B cells has been less studied, but genetic deficiency causes impairment of early and late developmental stagesObjectives To explore the role of autophagy in the pathogenesis of human and murine lupus, a disease in which B cells are critical effectors of pathology.Methods Autophagy was assessed using multiple techniques in NZB/W and control mice, and in patients with systemic lupus erythematosus (SLE) compared to healthy controls. We evaluated the phenotype of the B cell compartment in Vav-Atg7−/− mice in vivo, and examined human and murine plasmablast formation following inhibition of autophagy.Results We found activation of autophagy in early developmental and transitional stages of B cell development in a lupus mouse model even before disease onset, and which progressively increased with age. In human disease, again autophagy was activated compared with healthy controls, principally in naïve B cells. B cells isolated from Vav-Atg7F/F mice failed to effectively differentiate into plasma cells following stimulation in vitro. Similarly, human B cells stimulated in the presence of autophagy inhibition did not differentiate into plasmablasts.Conclusions Our data suggest activation of autophagy is a mechanism for survival of autoreactive B cells, and also demonstrate that it is required for plasmablast differentiation, processes that induce significant cellular stress. The implication of autophagy in two major pathogenic pathways in SLE suggests the potential to use inhibition of autophagy as a novel treatment target in this frequently severe autoimmune disease.
AU  - Clarke,AJ
AU  - Ellinghaus,U
AU  - Cortini,A
AU  - Stranks,A
AU  - Simon,AK
AU  - Botto,M
AU  - Vyse,TJ
DO  - 10.1136/annrheumdis-2013-204343
EP  - 920
PY  - 2015///
SN  - 0003-4967
SP  - 912
TI  - Autophagy is activated in systemic lupus erythematosus and required for plasmablast development
T2  - Annals of the Rheumatic Diseases
UR  - http://dx.doi.org/10.1136/annrheumdis-2013-204343
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352158500025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://ard.bmj.com/content/74/5/912
VL  - 74
ER  -
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