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2009 ; 183
(11
): 7104-18
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English Wikipedia
Apoptotic dendritic cells induce tolerance in mice through suppression of
dendritic cell maturation and induction of antigen-specific regulatory T cells
#MMPMID19917707
Kushwah R
; Oliver JR
; Zhang J
; Siminovitch KA
; Hu J
J Immunol
2009[Dec]; 183
(11
): 7104-18
PMID19917707
show ga
Dendritic cell (DC) apoptosis has been shown to play a role in maintaining a
balance between tolerance and immunity. However, the mechanisms of how DC
apoptosis affects the immune response are unclear. We have shown that in vitro
culture of apoptotic DCs with immature DCs, results in their uptake by immature
DCs, which subsequently turn into tolerogenic DCs, which then secrete TGF-beta1
and induce Foxp3(+) regulatory T cells (T(regs)). In this study we looked at the
effects of apoptotic DCs in vivo. Here we show that apoptotic DCs are taken up by
viable DCs in vivo, which suppresses the ability of viable DCs to undergo
maturation and subsequent migration to the lymph nodes in response to LPS.
Additionally, delivery of apoptotic DCs to LPS inflamed lungs results in
resolution of inflammation, which is mediated by the ability of apoptotic DCs to
suppress response of viable DCs to LPS. Additionally, apoptotic DCs also induce
TGF-beta1 secretion in the mediastinal lymph nodes, which results in expansion of
Foxp3(+) T(regs). Most importantly, we show that delivery of apoptotic DCs
followed by OVA in CFA to mice suppresses T cell response to OVA and instead
induces de novo generation of OVA-specific T(regs). Furthermore, delivery of
apoptotic DCs followed by OVA in CFA results in expansion of T(regs) in TCR
transgenic (OT-II) mice. These findings demonstrate that apoptotic DCs are taken
up by viable DCs in vivo, which promotes tolerance through suppression of DC
maturation and induction of T(regs).