Essential roles of S100A10 in Toll-like receptor signaling and immunity to infection
Toll-like receptors (TLRs) are key pattern recognition receptors that mediate innate immune responses to infection. However, uncontrolled TLR activation can lead to severe inflammatory disorders such as septic shock. The molecular mechanisms through which TLR responses are regulated are not fully un...
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Published in | Cellular & molecular immunology Vol. 17; no. 10; pp. 1053 - 1062 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
China
Nature Publishing Group
01.10.2020
Nature Publishing Group UK |
Subjects | |
Online Access | Get full text |
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Summary: | Toll-like receptors (TLRs) are key pattern recognition receptors that mediate innate immune responses to infection. However, uncontrolled TLR activation can lead to severe inflammatory disorders such as septic shock. The molecular mechanisms through which TLR responses are regulated are not fully understood. Here, we demonstrate an essential function of S100A10 in TLR signaling. S100A10 was constitutively expressed in macrophages, but was significantly downregulated upon TLR activation. S100A10-deficient macrophages were hyperresponsive to TLR stimulation, and S100A10-deficient mice were more sensitive to endotoxin-induced lethal shock and Escherichia coli-induced abdominal sepsis. Mechanistically, S100A10 regulated macrophage inflammatory responses by interfering with the appropriate recruitment and activation of the receptor-proximal signaling components and eventually inhibited TLR-triggered downstream signaling. These findings expand our understanding of TLR signaling and establish S100A10 as an essential negative regulator of TLR function and a potential therapeutic target for treating inflammatory diseases. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1672-7681 2042-0226 |
DOI: | 10.1038/s41423-019-0278-1 |