Handling Editor: Daniel Billadeau
ABSTRACT
Multinucleated giant cells (MGCs) are prominent in foreign body granulomas, infectious and inflammatory processes, and auto-immune, neoplastic and genetic disorders, but the molecular determinants that specify the formation and function of these cells are not defined. Here, using tandem mass tag-mass spectrometry, we identified a differentially upregulated protein, C-type lectin domain family 10 member (herein denoted CD301, also known as CLEC10A), that was strongly upregulated in mouse RAW264.7 macrophages and primary murine macrophages undergoing interleukin (IL-4)-induced MGC formation. CD301+ MGCs were identified in biopsy specimens of human inflammatory lesions. Function-inhibiting CD301 antibodies or CRISPR/Cas9 deletion of the two mouse CD301 genes (Mgl1 and Mgl2) inhibited IL-4-induced binding of N-acetylgalactosamine-coated beads by 4-fold and reduced MGC formation by 2.3-fold (P<0.05). IL-4-driven fusion and MGC formation were restored by re-expression of CD301 in the knockout cells. We conclude that in monocytes, IL-4 increases CD301 expression, which mediates intercellular adhesion and fusion processes that are required for the formation of MGCs.
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Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: P.J.B., M.G., C.A.M.; Methodology: P.J.B., Y.W., M.A.M., C.A.M.; Validation: P.J.B., Y.W., M.A.M., C.A.M.; Formal analysis: P.J.B., Y.W., M.A.M., C.A.M.; Investigation: P.J.B., C.A.M.; Resources: Y.W., C.A.M.; Data curation: P.J.B., C.A.M.; Writing - original draft: P.J.B., C.A.M.; Writing - review & editing: P.J.B., Y.W., C.A.M.; Visualization: P.J.B., Y.W.; Supervision: C.A.M.; Project administration: M.G., C.A.M.; Funding acquisition: M.G., C.A.M.
Funding
P.J.B. was supported by funding from a Queen Elizabeth II Graduate Scholarship in Science and Technology and Ontario Graduate Scholarships. C.A.M. is supported by a Canada Research Chair (Tier 1) in Matrix Dynamics. The research was funded by Canadian Institutes of Health Research (CIHR) grant MOP-142250 to M.G. and C.A.M., and an Alpha Omega Foundation of Canada Grant.
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.248864.supplemental
- Received May 14, 2020.
- Accepted November 9, 2020.
- © 2020. Published by The Company of Biologists Ltd
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