期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 51, 期 1, 页码 76-90出版社
WILEY
DOI: 10.1002/eji.201948413
关键词
alarmin; fibroblastic reticular cells; FRC; Interleukin-33; LCMV
类别
资金
- European Union's Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant [708715]
- Swiss National Science Foundation (SNF) Sinergia program [CRSII3_160772]
- SNF [166500]
- Marie Curie Actions (MSCA) [708715] Funding Source: Marie Curie Actions (MSCA)
- Swiss National Science Foundation (SNF) [CRSII3_160772] Funding Source: Swiss National Science Foundation (SNF)
Upon viral infection, stressed or damaged cells release IL-33 as endogenous danger signals to alert immune cells, mainly sourced from FRC and LEC cells. IL-33 plays a crucial role in antiviral T-cell responses, particularly in FRC.
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(+)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(+)T cells and their greatly augmented expansion in WT versusll33(-/-)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 naive T cells but also their expansion and differentiation several days into an antiviral response.
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