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 language | English (US) |
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Article number | 1502 |
Journal | Frontiers in immunology |
Volume | 8 |
Issue number | NOV |
DOIs | |
State | Published - Nov 8 2017 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 Elizondo, Andargie, Yang, Kacsinta and Lipscomb.
Keywords
- Dendritic cells
- Polarization
- Suppression
- T regulatory cells
- Tolerogenic