CLEC12B Regulates Melanocyte Immunity and Homeostasis in the Skin through the Signal Transducer and Activator of Transcription 1/IRF1 Axis

CLEC12B is a C-type lectin receptor involved in the inhibition of NKs-mediated cytotoxicity. We have previously shown that CLEC12B is predominantly expressed on melanocytes and inhibits melanin production and pigmentation as well as proliferation of melanoma. To date, the role of CLEC12B in skin immunity is unknown. Upon phosphorylation of its immunoreceptor tyrosine-based inhibitory motif, we demonstrate that CLEC12B increases the production of innate chemokines from human melanocytes through the activation of the signal transducer and activator of transcription 1/IFN regulatory factor 1-mediated IFNγ pathway, resulting in chemoattraction of immune cells. We have demonstrated CLEC12B to potentiate the effect of IFNγ in primed melanocytes. Furthermore, CLEC12B recognizes cutaneous (Staphylococcus aureus and E coli) but not gut (Listeria monocytogenes) bacteria and is capable of modulating their chemokine responses. Finally, we have shown that CLEC12B senses motifs present on human melanocytes and fibroblasts but not keratinocytes. Together, these results demonstrate that CLEC12B plays an important function in the human skin, bridging innate and adaptative immunity. This mechanism is of great interest because IFNγ and cellular recruitment are key initial steps involved in inflammation of many skin pathologies, making this receptor an interesting therapeutic target.

Authors

Institutions

Publication Details

Journal
Journal of Investigative Dermatology
Published
2024-12-28
DOI
https://doi.org/10.1016/j.jid.2024.11.016
Citations
1
Primary Topic
melanin and skin pigmentation
Type
article
Field-Weighted Citation Impact
0.33

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

CLEC12B Regulates Melanocyte Immunity and Homeostasis in the Skin through the Signal Transducer and Activator of Transcription 1/IRF1 Axis

Els Verhoeyen, M. Heim, Stéphane Rocchi, Meri K. Tulić et al.
1 citations
Journal of Investigative Dermatology
melanin and skin pigmentation
0.33
article

CLEC12B Regulates Melanocyte Immunity and Homeostasis in the Skin through the Signal Transducer and Activator of Transcription 1/IRF1 Axis

Els Verhoeyen, M. Heim, Stéphane Rocchi, Meri K. Tulić, Laura Sormani, Thierry Passeron, Bernd Lepenies, Lionel Larue, Yoann Rombouts, Odile Burlet‐Schiltz, Yann Chéli, Hanene Bzioueche, Lauriane Blot, Alexandre Stella
article en
1 citations

Abstract

CLEC12B is a C-type lectin receptor involved in the inhibition of NKs-mediated cytotoxicity. We have previously shown that CLEC12B is predominantly expressed on melanocytes and inhibits melanin production and pigmentation as well as proliferation of melanoma. To date, the role of CLEC12B in skin immunity is unknown. Upon phosphorylation of its immunoreceptor tyrosine-based inhibitory motif, we demonstrate that CLEC12B increases the production of innate chemokines from human melanocytes through the activation of the signal transducer and activator of transcription 1/IFN regulatory factor 1-mediated IFNγ pathway, resulting in chemoattraction of immune cells. We have demonstrated CLEC12B to potentiate the effect of IFNγ in primed melanocytes. Furthermore, CLEC12B recognizes cutaneous (Staphylococcus aureus and E coli) but not gut (Listeria monocytogenes) bacteria and is capable of modulating their chemokine responses. Finally, we have shown that CLEC12B senses motifs present on human melanocytes and fibroblasts but not keratinocytes. Together, these results demonstrate that CLEC12B plays an important function in the human skin, bridging innate and adaptative immunity. This mechanism is of great interest because IFNγ and cellular recruitment are key initial steps involved in inflammation of many skin pathologies, making this receptor an interesting therapeutic target.

Journal of Investigative DermatologyVol. 145(8)
Université Claude Bernard Lyon 1 (FR), Centre National de la Recherche Scientifique (FR), Université Toulouse III - Paul Sabatier (FR), Inserm (FR), The University of Queensland (AU), University of Veterinary Medicine Hannover, Foundation (DE), Université Côte d'Azur (FR), Centre Hospitalier Universitaire de Nice (FR), Max Planck Institute of Colloids and Interfaces (DE), Institut de Pharmacologie et de Biologie Structurale (FR), Institut de Biologie Valrose (FR), Centre Méditerranéen de Médecine Moléculaire (FR), Centre International de Recherche en Infectiologie (FR), Institut Curie (FR)
Institut National de la Santé et de la Recherche Médicale, Ligue Contre le Cancer, Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
Zero hunger
Openalex Percentile: Top 38%
melanin and skin pigmentation
0.33
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.