Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 140, Issue 9, Pages 1824-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2020.01.026
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Funding
- Milstein Medical Asian American Partnership Foundation
- CAMS Initiative for Innovative Medicine [2016-I2M-1-005, 2017-I2M-BR-14]
- National Natural Science Foundation of China [81371751, 81972950]
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Langhans multinucleated giant cells (LGCs) are a specific type of multinucleated giant cell containing a characteristic horseshoe-shaped ring of nuclei that are present within granulomas of infectious etiology. Although cytokines that trigger macrophage activation (such as IFN-gamma) induce LGC formation, it is not clear whether cytokines that trigger macrophage differentiation contribute to LGC formation. Here, we found that IL-15, a cytokine that induces M1 macrophage differentiation, programs human peripheral blood adherent cells to form LGCs. Analysis of the IL-15.treated adherent cell transcriptome identified gene networks for T cells, DNA damage and replication, and IFN-inducible genes that correlated with IL-15 treatment and LGC-type multinucleated giant cell formation. Gene networks enriched for myeloid cells were anticorrelated with IL-15 treatment and LGC formation. Functional studies revealed that T cells were required for IL-15.induced LGC formation, involving a direct contact with myeloid cells through CD40L-CD40 interaction and IFN-gamma release. These data indicate that IL-15 induces LGC formation through the direct interaction of activated T cells and myeloid cells.
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