in vivo

Laboratory for
Dendritic Cell Immunobiology
Team leader
Katsuaki Sato
Technical Staff
Student Trainee
Assistant
: Kaori Sato
Yumiko Sato
Kawori Eizumi
Tomohiro Fukaya
: Shigeharu Fujita
(RIKEN Junior Research Associate)
: Mai Yamamoto
Dendritic cells (DCs), the most potent of the
antigen (Ag)-presenting cells (APCs), were
originally defined by their dendritic morphology
but are now known to be heterogeneous, both in
terms of lineage, myeloid or lymphoid, as well as
maturity in both lymphoid and peripheral tissues.
Immature DCs (iDCs) sense the presence of
invading pathogens via various pattern recognition
receptors (PRRs) and process the pathogens
intracellularly in inflamed tissues, developing
into mature DCs (mDCs) characterized by
the upregulation of major histocompatibility
complex (MHC), and costimulatory molecules.
Subsequently, mDCs home into secondary
lymphoid tissues where they present the
processed Ags to naïve T cells to generate
effector T cells. Thereby, DCs play a crucial
role in the link between innate and adaptive
immunity. Accumulating indirect evidence
suggests that iDCs are involved in the
induction of peripheral tolerance under
steady-state conditions in vivo. On the other
hand, the modification of iDCs with certain
immunosuppressive molecules generates
tolerogenic DCs, which not only show a
reduced T-cell stimulatory capacity but also
induce anergic T cells and regulatory T (T R
) cells.
We have previously identified modified DCs
that have a capacity to produce anergic T cells
as well as T R cells than previously characterized
tolerogenic DCs. We have designated this
unique DC subset regulatory DCs (DC regs
). Our
goal is: (1) to clarify the molecular mechanisms
underlying the T-cell immunoregulatory function
of DC regs , (2) to develop immunotherapy with
DC regs for immunopathogenic diseases, and
(3) to characterize the specific DC subsets
involved in immune regulation.
Regulatory dendritic cells protect against
cutaneous chronic graft-versus-host
disease mediated through
CD4 + CD25 + Foxp3 + regulatory T cells
Chronic graft-versus-host disease (cGVHD)
is a common cause of morbidity and mortality
following allogeneic bone marrow transplantation
(alloBMT), however effective strategies for the
treatment of cGVHD have not been established.
In this study, we examined the therapeutic utility of
DC regs for cGVHD in a model of alloBMT in which
there is MHC compatibility but incompatibility
at multiple minor histocompatibility Ags.
Treatment of recipient mice following alloBMT
with recipient-type DC regs lead to greater
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