Fibroblast-derived IL-33 is dispensable for lymph node homeostasis but critical for CD8 T-cell responses to acute and chronic viral infection.

Details

Serval ID
serval:BIB_74E3A21E1736
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fibroblast-derived IL-33 is dispensable for lymph node homeostasis but critical for CD8 T-cell responses to acute and chronic viral infection.
Journal
European journal of immunology
Author(s)
Aparicio-Domingo P., Cannelle H., Buechler M.B., Nguyen S., Kallert S.M., Favre S., Alouche N., Papazian N., Ludewig B., Cupedo T., Pinschewer D.D., Turley S.J., Luther S.A.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
22/07/2020
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Upon viral infection, stressed or damaged cells can release alarmins like IL-33 that act as endogenous danger signals alerting innate and adaptive immune cells. IL-33 coming from nonhematopoietic cells has been identified as important factor triggering the expansion of antiviral CD8 <sup>+</sup> T cells. In LN the critical cellular source of IL-33 is unknown, as is its potential cell-intrinsic function as a chromatin-associated factor. Using IL-33-GFP reporter mice, we identify fibroblastic reticular cells (FRC) and lymphatic endothelial cells (LEC) as the main IL-33 source. In homeostasis, IL-33 is dispensable as a transcriptional regulator in FRC, indicating it functions mainly as released cytokine. Early during infection with lymphocytic choriomeningitis virus (LCMV) clone 13, both FRC and LEC lose IL-33 protein expression suggesting cytokine release, correlating timewise with IL-33 receptor expression by reactive CD8 <sup>+</sup> T cells and their greatly augmented expansion in WT versus ll33 <sup>-/-</sup> mice. Using mice lacking IL-33 selectively in FRC versus LEC, we identify FRC as key IL-33 source driving acute and chronic antiviral T-cell responses. Collectively, these findings show that LN T-zone FRC not only regulate the homeostasis of naïve T cells but also their expansion and differentiation several days into an antiviral response.
Keywords
FRC, Interleukin-33, LCMV, alarmin, fibroblastic reticular cells
Pubmed
Create date
11/08/2020 10:59
Last modification date
02/09/2020 5:26
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