Necroptosis of dendritic cells promotes activation of γδ T cells

Cheryl C. Collins, Kathleen Bashant, Cuixia Erikson, Phyu Myat Thwe, Karen A. Fortner, Hong Wang, Craig T. Morita, Ralph C. Budd

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

γδ T cells function at the interface between innate and adaptive immunity and have well-demonstrated roles in response to infection, autoimmunity and tumors. A common characteristic of these seemingly disparate conditions may be cellular stress or death. However, the conditions under which ligands for γδ T cells are induced or exposed remain largely undefined. We observed that induction of necroptosis of murine or human dendritic cells (DC) by inhibition of caspase activity paradoxically augments their ability to activate γδ T cells. Furthermore, upregulation of the stabilizer of caspase-8 activity, c-FLIP, by IL-4, not only greatly reduced the susceptibility of DC to necroptosis, but also considerably decreased their ability to activate γδ T cells. Collectively, these findings suggest that the induction of necroptosis in DC upregulates or exposes the expression of γδ T cell ligands, and they support the view that γδ T cells function in the immune surveillance of cell stress.

Original languageEnglish (US)
Pages (from-to)479-492
Number of pages14
JournalJournal of Innate Immunity
Volume8
Issue number5
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • c-FLIP
  • Caspases
  • Dendritic cells
  • Necroptosis
  • γδ T cells

ASJC Scopus subject areas

  • Immunology and Allergy

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