signaling lymphocyte activation molecule family 5 enhances autophagy and fine-tunes cytokine response in monocyte-derived dendritic cells via stabilization of interferon regulatory factor 8
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2018
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Abstract
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-1β, IL-23, and IL-12 production in LPS/IFNγ-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.
| Reference Key |
agod2018frontierssignaling
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| Authors | ;Zsofia Agod;Kitti Pazmandi;Dora Bencze;Gyorgy Vereb;Tamas Biro;Attila Szabo;Attila Szabo;Eva Rajnavolgyi;Eva Rajnavolgyi;Attila Bacsi;Attila Bacsi;Pablo Engel;Arpad Lanyi;Arpad Lanyi |
| Journal | sudebno-meditsinskaia ekspertiza |
| Year | 2018 |
| DOI |
10.3389/fimmu.2018.00062
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| URL | |
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