⮝ Full datasets listing
PXD075217
PXD075217 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Siglec-7 inhibits TLR3-induced pro-inflammatory cytokine production from human monocytes and macrophages |
| Description | Immune checkpoint receptors, including Sialic-acid-binding immunoglobulinlike lectins (Siglecs), are critical regulators of immune homeostasis. Siglecs can serve as negative regulators of Toll-like receptor (TLR) signaling, promoting the resolution of inflammatory signaling through feedback inhibition mechanisms. Previous studies demonstrated that Siglec-E, the murine homolog of the human inhibitory receptor Siglec-7, negatively regulates TLR4 signaling by controlling receptor endocytosis. This regulatory mechanism suggests that Siglec-7 may also limit TLR signaling. Here we reveal a novel mechanism whereby Siglec-7 represses endosomal TLR3 activation, compared to other TLRs, in human myeloid cells. Crosslinking Siglec-7 with antibody clone QA79 significantly reduced TNFa secretion in U937 cells, primary monocytes, and macrophages following Poly(I:C) stimulation. Mechanistically, QA79 triggers rapid FcgRindependent internalization and endolysosomal trafficking of surface Siglec-7, which enables the direct co-localization of Siglec-7 with TLR3 within the endolysosome. This co-localization between Siglec-7 and TLR3 suppresses NFkB phosphorylation, a key pro-inflammatory signaling node downstream of TLR3. These findings establish a previously unrecognized negative regulatory role of Siglec-7 for TLR3-mediated inflammation in myeloid cells, where a disrupted interaction could contribute to autoimmune disease pathogenesis. Targeting this pathway represents a promising therapeutic approach for TLR3-driven autoimmune diseases. |
| HostingRepository | jPOST |
| AnnounceDate | 2026-03-05 |
| AnnouncementXML | Submission_2026-03-05_07:51:08.184.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Bo Yang |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
| ModificationList | S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide |
| Instrument | instrument |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-03-04 09:35:07 | ID requested | |
| ⏵ 1 | 2026-03-05 07:51:08 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: siglec-7, DIA, TLR3-mediated inflammation |
Contact List
| Bo Yang | |
|---|---|
| lab head | |
| Bo Yang | |
| contact affiliation | Sanofi |
| dataset submitter | |
Full Dataset Link List
| jPOST dataset URI |
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