Summary
A bioRxiv preprint reports that Clec18a dampened inflammatory responses in cell and mouse experiments. The authors propose that it acts through Mincle, TRPM7-dependent calcium entry and the enzyme Cbl.
A bioRxiv preprint reports that the soluble immune protein Clec18a can dampen early inflammatory responses in cell and mouse experiments. The researchers propose that it does so by binding the immune receptor Mincle and activating a pathway involving the TRPM7 ion channel and the enzyme Cbl.
The authors report that Clec18a levels rise in several inflammatory diseases, including sepsis and influenza, and that immune cells—including macrophages, dendritic cells and T cells—release it within minutes of activation. In mice, removing Clec18a from myeloid cells was associated with lower survival and more severe inflammation than in wild-type mice. Adding recombinant Clec18a reduced inflammation in experiments conducted both in vitro and in vivo.
A proposed route from receptor binding to immune suppression
The proposed mechanism begins when Clec18a binds Mincle, a C-type lectin receptor. That interaction triggers calcium entry into cells through TRPM7, according to the preprint. The calcium signal activates Cbl, an E3 ubiquitin ligase—a type of enzyme that attaches ubiquitin to proteins and can help direct them toward degradation.
The authors report that the pathway leads to formation and degradation of a complex involving Mincle, Cbl, the signalling adaptor MyD88 and TRPM7. MyD88 is also involved in Toll-like receptor signalling, so the proposed mechanism links two receptor systems involved in innate immunity.
Several experimental interventions supported the proposed pathway: Cbl deficiency, calcium inhibition or TRPM7 knockdown each eliminated Clec18a-mediated immune suppression. Together, the findings suggest that Clec18a acts as a regulatory brake on the initiation of innate immune responses.
The work is a preprint describing cell and mouse experiments, not clinical testing. The abstract does not specify the disease models, sample sizes or effect estimates, so the scale and reach of the reported effects cannot be assessed from the available study summary.