Last update 01 Nov 2024

CLEC12B

Last update 01 Nov 2024

Basic Info

Synonyms

C-type lectin domain family 12 member B, CLEC12B, Macrophage antigen H

Introduction

Inhibitory receptor postulated to negatively regulate immune and non-immune functions (PubMed:17562706, PubMed:34310951). Upon phosphorylation, recruits SH2 domain-containing PTPN6 and PTPN11 phosphatases to its ITIM motif and antagonizes activation signals (PubMed:17562706, PubMed:34310951). Although it inhibits KLRK1/NKG2D-mediated signaling, it does not bind known ligands of KLRK1/NKG2D and therefore is not its inhibitory counterpart (PubMed:17562706). May limit activation of myeloid cell subsets in response to infection or tissue inflammation (PubMed:17562706). May protect target cells against natural killer cell-mediated lysis (PubMed:17562706). May negatively regulate cell cycle and differentiation of melanocytes via inactivation of STAT3 (PubMed:34310951).

Drugs associated with CLEC12B

WO2022215566

Patent Mining

Target

CLEC12B

Mechanism-

Active Org.

University of Tsukuba

Originator Org.

University of Tsukuba

Active Indication

Skin Diseases, Genetic

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CLEC12B

100 Translational Medicine associated with CLEC12B

0 Patents (Medical) associated with CLEC12B

Literatures (Medical) associated with CLEC12B

01 Jun 2023·Journal of medical microbiology

CLEC4A and CLEC12B C-type lectin receptors mediate interactions with Pneumocystis cell wall components.

Article

Author: Limper, Andrew H ; Kottom, Theodore J ; Carmona, Eva M ; Schaefbauer, Kyle

Introduction. C-type lectin receptors (CLRs) are prominently expressed on myeloid cells where they perform multiple functions including serving as pattern recognition receptors (PRRs) to drive innate as well as adaptive immunity to pathogens. Depending on the presence of a tyrosine-based signalling motif, CLR-microbial pathogen engagement may result in either anti- or pro-inflammatory signalling.Impact statement. In this manuscript, we report our laboratory study of two novel CLRs that recognize Pneumocystis murina cell wall homogenates (CWH) and a purified Pneumocystis carinii cell wall fraction (CWF).Aim. To study the potential of newly generated hFc-CLR fusions on binding to Pneumocystis murina CWHs and P. carinii CWFs and subsequent downstream inflammatory signalling analysis.Methods. Newly generated hFc-CLR fusion CLEC4A and CLEC12B were screened against P. murina CWHs and P. carinii CWFs preparations via modified ELISA. Immunofluorescence assay (IFA) was utilized to visualize hFc-CLR fusion binding against intact fixed fungal life forms to verify results. Quantitative PCR (q-PCR) analysis of lung mRNA from the mouse immunosuppressed Pneumocystis pneumonia (PCP) model versus uninfected mice was employed to detect possible changes in the respective Clec4a and Clec12b transcripts. Lastly, siRNA technology of both CLRs was conducted to determine effects on downstream inflammatory events in mouse macrophages stimulated in the presence of P. carinii CWFs.Results. We determined that both CLEC4A and CLEC12B hFc-CLRs displayed significant binding with P. murina CWHs and P. carinii CWFs. Binding events showed significant binding to both curdlan and laminarin, both polysaccharides containing β-(1,3) glucans as well as N-acetylglucosamine (GlcNAc) residues and modest yet non-significant binding to the negative control carbohydrate dextran. IFA with both CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of both CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that both CLRs were significantly up regulated during infection. Lastly, siRNA of both CLRs in the mouse RAW macrophage cell line was conducted and results demonstrated that silencing of Clec4a resulted in no significant changes in TNF-alpha generation in P. carinii CWF stimulated macrophages. On the contrary, silencing of Clec12b CLR resulted in significant decreases in TNF-alpha in RAW cells stimulated with the same CWF.Conclusion. The data presented here provide new members of the CLRs family recognizing Pneumocystis. Future studies using CLEC4A and/or CLEC12B deficient mice in the PCP mouse model should provide further insights into the host immunological response to Pneumocystis.

01 Dec 2022·Fish & Shellfish Immunology

A novel C-type lectin (CLEC12B) from Nile tilapia (Oreochromis niloticus) is involved in host defense against bacterial infection

Article

Author: Jiang, Baijian ; Huang, Yongxiong ; Li, Qi ; Zhang, Zhiqiang ; Huang, Yu ; Jian, Jichang ; Niu, Jinzhong ; Li, Xing

C-type lectin (CLEC) is a family of carbohydrate-binding protein that has high affinity for calcium and mediates multiple biological events including adhesion between cells, the turnover of serum glycoproteins, and the innate immune system's reaction to prospective invaders. However, it's ill-defined for how CLEC effects bony fish's innate immunity to bacterial infection. Therefore, CLEC12B, a member of the C-type lectin domain family, was found in Nile tilapia (Oreochromis niloticus) and its functions in bacterial infection were examined. The OnCLEC12B consist of a C-type lectin domain, a transmembrane domain, and a hypothetical protein of 308 amino acids that encoded by 927 bp basic group. Besides, the OnCLEC12B protein have a series of highly conserved amino acid sites with other CLEC12B proteins. Subcellular localization showed that OnCLEC12B located in cell membrane. Transcriptional levels investigation showed that OnCLEC12B was extensively expressed in all selected organs and has high expression in the liver. The transcriptional levels of OnCLEC12B were induced by Streptococcus agalactiae and Aeromonas hydrophila in the liver, spleen, head kidney, brain, and intestine. Afterward, invitro study revealed that several kinds of pathogens could be bound and agglutinated by recombinant protein of OnCLEC12B (rOnCLEC12B). Moreover, rOnCLEC12B could not only promote the proliferation of monocytes/macrophages but also encourage its phagocytosis on S.agalactiae and A.hydrophila, and its over-expression could significantly suppress the activation of the NF-κB pathway. Summarily, our results indicated that OnCLEC12B gets involved in fish immunization activities to pathogens infection.

01 Jul 2022·Journal of Investigative DermatologyQ1 · MEDICINE

CLEC12B Is a Melanocytic Gene Regulating the Color of the Skin

Q1 · MEDICINE

Article

Author: Cheli, Yann ; Sormani, Laura ; Mhaidly, Rana ; Taquin Martin, Hélène ; Rocchi, Stéphane ; Heim, Marjorie ; De Donatis, Gian Marco ; Blot, Lauriane ; Nottet, Nicolas ; Dabert Gay, Anne Sophie ; Cardot Leccia, Nathalie ; Debayle, Delphine ; Gesbert, Franck ; Montaudie, Henri ; Passeron, Thierry ; Tulic, Meri K ; Regazzetti, Claire ; Verhoeyen, Els

Pigmentation of the human skin is a complex process regulated by many genes. However, only a few have a profound impact on melanogenesis. Transcriptome analysis of pigmented skin compared with analysis of vitiligo skin devoid of melanocytes allowed us to unravel CLEC12B as a melanocytic gene. We showed that CLEC12B, a C-type lectin receptor, is highly expressed in melanocytes and that its expression is decreased in dark skin compared with that in white skin. CLEC12B directly recruits and activates SHP1 and SHP2 through its immunoreceptor tyrosine-based inhibitory motif domain and promotes CRE-binding protein degradation, leading to the downregulation of the downstream MITF pathway. CLEC12B ultimately controls melanin production and pigmentation in vitro and in a model of reconstructed human epidermis. The identification of CLEC12B in melanocytes shows that C-type lectin receptors exert function beyond immunity and inflammation. It also provides insights into the understanding of melanocyte biology and regulation of melanogenesis.

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CLEC12B

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