Type I interferon induces CXCL13 to support ectopic germinal center formation
File(s)
Author(s)
Type
Journal Article
Abstract
Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation.
Date Issued
2019-02-05
Date Acceptance
2019-01-17
Citation
Journal of Experimental Medicine, 2019, 216 (3), pp.621-637
ISSN
0022-1007
Publisher
Rockefeller University Press
Start Page
621
End Page
637
Journal / Book Title
Journal of Experimental Medicine
Volume
216
Issue
3
Copyright Statement
© 2019 Denton et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the
publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0
International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0
International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
Sponsor
BBSRC
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000460464100015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
BB/N011740/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
LYMPHOID-TISSUE IBALT
B-CELL RECEPTOR
INFLUENZA-VIRUS
T-CELL
C-MYC
CHEMOKINE RECEPTOR
INNATE IMMUNITY
RESPONSES
ABSENCE
MEMORY
Publication Status
Published
Date Publish Online
2019-02-05