[HTML][HTML] In Vivo Induction of Tr1 Cells via Mucosal Dendritic Cells and AHR Signaling

HY Wu, FJ Quintana, AP da Cunha, BT Dake… - PloS one, 2011 - journals.plos.org
HY Wu, FJ Quintana, AP da Cunha, BT Dake, T Koeglsperger, SC Starossom, HL Weiner
PloS one, 2011journals.plos.org
Background Type 1 regulatory T (Tr1) cells, characterized by the secretion of high levels of
the anti-inflammatory cytokine interleukin-10 (IL-10), play an important role in the regulation
of autoimmune diseases and transplantation. However, effective strategies that specifically
induce Tr1 cells in vivo are limited. Furthermore, the pathways controlling the induction of
these cells in vivo are not well understood. Methodology/Principal Findings Here we report
that nasal administration of anti-CD3 antibody induces suppressive Tr1 cells in mice. The in …
Background
Type 1 regulatory T (Tr1) cells, characterized by the secretion of high levels of the anti-inflammatory cytokine interleukin-10 (IL-10), play an important role in the regulation of autoimmune diseases and transplantation. However, effective strategies that specifically induce Tr1 cells in vivo are limited. Furthermore, the pathways controlling the induction of these cells in vivo are not well understood.
Methodology/Principal Findings
Here we report that nasal administration of anti-CD3 antibody induces suppressive Tr1 cells in mice. The in vivo induction of Tr1 cells by nasal anti-CD3 is dependent on IL-27 produced by upper airway resident dendritic cells (DCs), and is controlled by the transcription factors aryl hydrocarbon receptor (AHR) and c-Maf. Subsequently, IL-21 acts in an autocrine fashion to expand and maintain the Tr1 cells induced in vivo by nasally administered anti-CD3.
Conclusions/Significance
Our findings identify a unique approach to generate Tr1 cells in vivo and provide insights into the mechanisms by which these cells are induced.
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