Inhibition of allograft inflammatory factor-1 in dendritic cells restrains CD4+ T cell effector responses and induces CD25+Foxp3+ T regulatory subsets

Diana M. Elizondo, Temesgen E. Andargie, Dazhi Yang, Apollo D. Kacsinta, Michael W. Lipscomb

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca2+ binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports that AIF1 is expressed in CD11c+ dendritic cells (DC) and silencing of expression restrains induction of antigen-specific CD4+ T cell effector responses. AIF1 knockdown in murine DC resulted in impaired T cell proliferation and skewed polarization away from T helper type 1 and 17 fates. In turn, there was a parallel expansion of IL-10-producing and CD25+Foxp3+ T regulatory subsets. These studies are the first to demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and presents a novel target for engineering tolerogenic DC-based immunotherapies.

Original languageEnglish (US)
Article number1502
JournalFrontiers in immunology
Volume8
Issue numberNOV
DOIs
StatePublished - Nov 8 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elizondo, Andargie, Yang, Kacsinta and Lipscomb.

Keywords

  • Dendritic cells
  • Polarization
  • Suppression
  • T regulatory cells
  • Tolerogenic

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