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Cellular, Molecular, and Immunological Characteristics of Langhans Multinucleated Giant Cells Programmed by IL-15

Hongsheng Wang1, Haiqin Jiang2, Rosane M B Teles3

  • 1Department of Medicine, Division of Dermatology, David Geffen School of Medicine at University of California (UCLA), Los Angeles, California, USA; Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

The Journal of Investigative Dermatology
|February 25, 2020
PubMed

Insights

Interleukin-15 (IL-15) promotes the formation of Langhans multinucleated giant cells (LGCs) by programming myeloid cells. This process requires direct T cell and myeloid cell interaction, highlighting a novel pathway for LGC development.

Area of Science:

  • Immunology
  • Cell Biology
  • Infectious Diseases

Background:

  • Langhans multinucleated giant cells (LGCs) are characteristic of infectious granulomas.
  • Cytokines like IFN-γ induce macrophage activation and LGC formation.
  • The role of differentiation-inducing cytokines in LGC formation is unclear.

Purpose of the Study:

  • To investigate whether IL-15, a macrophage differentiation cytokine, contributes to LGC formation.
  • To elucidate the molecular mechanisms underlying IL-15-induced LGC development.

Main Methods:

  • Treatment of human peripheral blood adherent cells with IL-15.
  • Transcriptome analysis to identify gene expression patterns.
  • Functional studies involving T cell-myeloid cell co-cultures and interaction blocking.

Main Results:

  • IL-15 induced LGC formation in human peripheral blood adherent cells.
  • Transcriptome analysis revealed T cell, DNA damage, and IFN-inducible gene networks correlated with LGC formation.
  • T cell-myeloid cell contact via CD40L-CD40 and IFN-γ release were essential for IL-15-induced LGCs.

Conclusions:

  • IL-15 programs myeloid cells to form LGCs.
  • IL-15-induced LGC formation is dependent on T cell-myeloid cell interactions.
  • This study reveals a novel mechanism for LGC formation involving IL-15 and T cell activation.

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