Network analysis identifies proinflammatory plasma cell polarization for secretion of ISG15 in human autoimmunity

Care, M.A., Stephenson, S.J., Barnes, N.A., Fan, I., Zougman, A., El-Sherbiny, Y.M. ORCID: 0000-0003-4791-3475, Vital, E.M., Westhead, D.R., Tooze, R.M. and Doody, G.M., 2016. Network analysis identifies proinflammatory plasma cell polarization for secretion of ISG15 in human autoimmunity. The Journal of Immunology, 197 (4), pp. 1447-1459. ISSN 0022-1767

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Abstract

Plasma cells (PCs) as effectors of humoral immunity produce Igs to match pathogenic insult. Emerging data suggest more diverse roles exist for PCs as regulators of immune and inflammatory responses via secretion of factors other than Igs. The extent to which such responses are preprogrammed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. In this study, we dissect the impact of IFNs on the regulatory networks of human PCs. We show that core PC programs are unaffected, whereas PCs respond to IFNs with distinctive transcriptional responses. The IFN-stimulated gene 15 (ISG15) system emerges as a major transcriptional output induced in a sustained fashion by IFN-α in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active systemic lupus erythematosus. Thus, ISG15-secreting PCs represent a distinct proinflammatory PC subset providing an Ig-independent mechanism of PC action in human autoimmunity.

Item Type: Journal article
Publication Title: The Journal of Immunology
Creators: Care, M.A., Stephenson, S.J., Barnes, N.A., Fan, I., Zougman, A., El-Sherbiny, Y.M., Vital, E.M., Westhead, D.R., Tooze, R.M. and Doody, G.M.
Publisher: American Association of Immunologists
Date: 15 August 2016
Volume: 197
Number: 4
ISSN: 0022-1767
Identifiers:
NumberType
10.4049/jimmunol.1600624DOI
Rights: This is an open-access article distributed under the terms of the CC-BY 3.0 Unported license.
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 22 Feb 2019 10:21
Last Modified: 22 Feb 2019 10:26
URI: http://irep.ntu.ac.uk/id/eprint/35794

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