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Last update 08 May 2025

SIGLEC14

Last update 08 May 2025

Basic Info

Synonyms

sialic acid binding Ig like lectin 14, Sialic acid-binding Ig-like lectin 14, Siglec-14

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Introduction

Putative adhesion molecule. Sialic acid-binding paired receptor which may activate associated receptors.

Drugs associated with SIGLEC14

CN119158045

Patent Mining

Target

SIGLEC14

Mechanism-

Active Org.

Guangxi Medical University

Originator Org.

Guangxi Medical University

Active Indication

Infectious Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SIGLEC14

100 Translational Medicine associated with SIGLEC14

0 Patents (Medical) associated with SIGLEC14

Literatures (Medical) associated with SIGLEC14

21 Apr 2025·ACS Applied Bio Materials

Siglec-14-Mediated Inflammatory Responses to Carbon Nanomaterials

Article

Author: Nakayama, Masafumi ; Takemura, Miki ; Yamaguchi, Shin-Ichiro ; Miwa, Karen ; Morimoto, Nobuyuki

Carbon nanomaterials (CNM), including carbon nanotubes (CNT) and graphene nanoplatelets (GNP), are expected to have diverse industrial applications due to their unique physical properties. However, concerns have been raised regarding their toxicity in humans. In this context, risk assessment must include an understanding of the molecular mechanisms underlying human recognition of CNM. We have recently identified human sialic acid-binding immunoglobulin-like lectin (Siglec)-14 as a CNT-recognizing receptor. Since no rodent orthologs for Siglec-14 exist, previous rodent toxicological studies may underestimate CNM toxicity in humans. Therefore, in this study, we investigate Siglec-14 responses to various CNM. Siglec-14 recognizes various types of CNM via its extracellular aromatic cluster with a similar affinity, regardless of size and shape. Ultrathin single-walled CNT (SWCNT) and spherical carbon black nanoparticles (CBNP) activated macrophage Siglec-14 signaling, leading to IL-8 production. Notably, GNP as well as long needle-like MWCNT not only activate this inflammatory signal but also cause phagosomal damage, leading to the release of IL-1β, the most prominent pro-inflammatory cytokine. In mice transduced with Siglec-14, intratracheal injection of GNP or long needle-like MWCNT caused lung inflammation, whereas injection of SWCNT or CBNP did not. Taken together, these results suggest that CNM-induced inflammation requires two processes: macrophage receptor ligation and phagosomal damage. This indicates that CNM may be safe unless they cause damage to the macrophage phagosome.

01 Apr 2025·International Journal of Biological Macromolecules

Forsythoside B activates Siglec-14 to inhibit HIV-1 replication via the JAK1/STAT1 pathway

Article

Author: Ye, Li ; Su, Jinming ; Yuan, Zongxiang ; Hu, Xiaopeng ; Jiang, Junjun ; Liu, Jie ; Chen, Rongfeng ; Chen, Feirong ; Chen, Shanshan ; An, Sanqi ; Liang, Hao ; Wei, Wudi

The HIV/AIDS epidemic poses a severe global health challenge. While antiretroviral therapy is crucial, it has limitations, including high costs and resistance, and requires long-term use. Consequently, novel antiviral agents with unique structures and innovative mechanisms are needed for better management of HIV/AIDS. We previously discovered that Siglec-14 inhibits HIV-1 replication. In this study, we employed homology modeling and AlphaFold 2 to predict the structure of Siglec-14, followed by molecular dynamics simulations to explore its conformational landscape. The MM/GBSA method was used to calculate the binding free energy of selected small molecules. Among them, Forsythoside B (FTS·B) exhibited the highest binding free energy and enhanced Siglec-14's conformational stability. SPR analysis further confirmed a strong binding affinity between FTS·B and Siglec-14. In vitro experiments demonstrated that FTS·B upregulates Siglec-14 expression and suppresses HIV-1 replication in macrophages. Mechanistically, FTS·B suppresses pro-inflammatory cytokines, increases the expression of interferon-stimulated genes and chemokines, and activates the JAK1/STAT1 pathway in Siglec-14 knockdown macrophages. Our results confirm that FTS·B, as an agonist of Siglec-14, effectively inhibits HIV-1 replication by upregulating Siglec-14 expression and modulating the JAK1/STAT1 signaling pathway, highlighting the potential clinical application value of FTS·B in HIV treatment.

01 Dec 2024·Fish & Shellfish Immunology

Functional characterization of Siglec14 in facilitating innate defenses in Carassius cuvieri × Carassius auratus red var

Article

Author: Zeng, Qiongyao ; Zhou, Zejun ; Li, Pingyuan ; Wei, Zehong ; Liu, Yujun ; Tang, Yiyang ; Yang, Ye

Sialic acid-binding Ig-like lectin 14 (Siglec14) is a member of the Siglecs family, a group of immune system receptors characterized by their ability to recognize sialic acids, which are a type of carbohydrate commonly found on the surfaces of cells in mammals. However, the role of Siglec14 in the innate immunity of teleosts has not been extensively explored. For this purpose, our study focused on the identification and characterization of a classical Siglec14, designated as WR-Siglec14, derived from the hybrid fish Carassius cuvieri × Carassius auratus red var. Sequence analysis reveals WR-Siglec14 has the considerable homology with Siglec14 orthologs across various species, featuring the conserved immunoglobulin domains. We further investigated the expression patterns of WR-Siglec14 in response to pathogen exposure and observed significant upregulation in key immune-related tissues upon infection with Aeromonas hydrophila. Additionally, the study demonstrated that WR-Siglec14 enhanced the bactericidal activity and interacted with WR-DAP12. Moreover, we found treatment with WR-Siglec14 maintained higher numbers of goblet cells and mitigated apoptosis in the gut tissue during A. hydrophila infection. WR-Siglec14 also stimulated antimicrobial gene expression and reduced bacterial burdens in the fish, significantly improving survival rates against A. hydrophila infection. These results indicate that WR-Siglec14 plays the critical role in immune defense and gut barrier function against pathogen invasion in fish.

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SIGLEC14

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