期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00062
关键词
SLAMF5; autophagy; dendritic cell; IRF8; TRIM21; IL-12p70; LPS/IFN gamma
类别
资金
- Janos Bolyai Research Scholarship from the Hungarian Academy of Sciences
- EU Framework Program Horizon
- European Union
- European Regional Development Fund
- Romanian Ministry of Education, Executive Agency For Higher Education, Research, Development and Innovation Funding, PNCDI II [119/2014]
- National Research, Development and Innovation Office (NKFIH) [K-81676, K-109444]
- [GINOP-2.3.2-15-2016-00050]
Signaling lymphocyte activation molecule family (SLAMF) receptors are essential regulators of innate and adaptive immune responses. The function of SLAMF5/CD84, a family member with almost ubiquitous expression within the hematopoietic lineage is poorly defined. In this article, we provide evidence that in human monocyte-derived dendritic cells (moDCs) SLAMF5 increases autophagy, a degradative pathway, which is highly active in dendritic cells (DCs) and plays a critical role in orchestration of the immune response. While investigating the underlying mechanism, we found that SLAMF5 inhibited proteolytic degradation of interferon regulatory factor 8 (IRF8) a master regulator of the autophagy process by a mechanism dependent on the E3-ubiquitin ligase tripartite motif-containing protein 21 (TRIM21). Furthermore, we demonstrate that SLAMF5 influences the ratio of CD1a(+) cells in differentiating DCs and partakes in the regulation of IL-1 beta, IL-23, and IL-12 production in LPS/IFN gamma-activated moDCs in a manner that is consistent with its effect on IRF8 stability. In summary, our experiments identified SLAMF5 as a novel cell surface receptor modulator of autophagy and revealed an unexpected link between the SLAMF and IRF8 signaling pathways, both implicated in multiple human pathologies.
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