Submitted March 16, 2006
Accepted April 24, 2006
Tolerogenic dendritic cells: Cytokine modulation comes of age
Sergio Rutella*, Silvio Danese, and Giuseppe Leone
Department of Hematology, Catholic University Medical School, Rome, Italy
Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano, Milan, Italy
* Corresponding author; email: srutella{at}rm.unicatt.it.
Dendritic cells (DCs) include a heterogeneous family of
professional APCs involved in initiation of immunity and
in immunological tolerance. Specifically, peripheral
tolerance can be achieved and maintained by promoting
regulatory T cell (Treg) responses and/or T-cell anergy or
deletion. Until recently, immature developmental stages of
DC differentiation were believed to induce T-cell anergy
or Treg cells, whereas DCs transformed into mature DCs by
activation stimuli were thought to represent immunogenic
DCs capable of inciting primary T-cell responses.
This paradigm has been challenged by the demonstration of
Treg-cell expansion by antigen-bearing, fully mature DCs.
Similarly, semi-mature DCs with a distinctive
IL-10+IL-12- cytokine production
profile might be endowed with tolerogenic functions,
supporting the concept that DC maturation per se should no
longer be considered as a distinguishing feature of
immunogenic as opposed to tolerogenic DCs (TDCs).
Cytokine-modulated TDCs reflect an incomplete or altered
status of monocyte differentiation and promote in vitro
induction of Treg cells and/or in vivo protection from
autoimmune diseases. Several growth factors, including
IL-10, TGF-
, G-CSF, HGF and VIP modulate DC
maturation and favor the differentiation of TDCs. From a
therapeutic standpoint, cytokine-modulated TDCs might be
beneficial for prevention and/or treatment of
post-transplantation GVHD and autoimmunity.
