Table 1.

Recent advances in DC biology, tolerogenic DCs, and pharmacological conditioning protocols.

	Authors	Reference
Tolerogenic DCs
Constitutive ablation of DCs breaks self-tolerance of CD4+ T cells leading to fatal autoimmunity	Ohnmacht et al.	[19]
Tolerogenic DCs favor graft tolerance through interferon-γ and Epstein-Barr virus-induced gene 3	Hill et al.	[20]
Tolerogenic DCs generated with immunosuppressive cytokines induce antigen-specific anergy and regulatory properties in memory CD4+ T cells	Torres-Aguilar et al.	[21]
DC genealogy
DC and monocyte lineages originate from a common progenitor that gives rise to monocytes and committed DC progenitors, which give rise to lymphoid tissue DCs and nonlymphoid tissue DCs	Liu and Nussenzweig	[22]
DCs in mouse lymphoid organs in the steady state are monocyte independent and require Flt3L for their development. Other tissue may contain additional M-CSF-dependent monocytes	Steinman and Idoyaga	[23]
The differing origins of gut DCs may explain how the intestinal immune system manages to destroy harmful pathogens while tolerating beneficial bacteria	Laffont and Powrie	[24]
Comparative genomics reveals functional equivalences between human and mouse DC subsets	Crozat et al.	[25]
Plasmacytoid DCs (pDCs)
Compared to conventional DCs, pDCs show reduced costimulatory molecule expression and poor T-cell allostimulatory capacity. Under homeostatic conditions, nonlymphoid tissue-resident pDCs regulate mucosal immunity and the development of both central and peripheral tolerance	Rogers et al.	[26]
Human pDCs preferentially express immunoglobulin-like transcript 7 (ILT7), which activates an immunoreceptor tyrosine-based activation motif- (ITAM-) mediated signaling pathway	Cao and Bover	[27]
Pharmacological DC conditioning
Rapamycin-conditioned, alloantigen-pulsed DCs present donor MHC class I-peptide via the semidirect pathway and inhibit survival of antigen-specific CD8(+) T cells	Thomson et al. and Fischer et al.	[28, 29]
Human rapamycin-treated DCs are only partially maturation resistant in vivo	Macedo et al.	[30]
Adenosine A2AR agonist-conditioned DCs attenuate acute renal ischemia-reperfusion injury	Li et al.	[31]
Vitamin D3-conditioned DCs induce effector T-cell apoptosis and antigen-specific Tregs	Nikolic and Roep	[32]
Role of conventional DCs of the recipient in tolerogenic DC therapy
Depleting recipient DCs at the time of tolerogenic DC therapy abrogates its beneficial effect	Divito et al., Wang et al.	[33, 34]
Role of exosomes
Exosomes mediate transfer of functional microRNAs between mouse DCs	Montecalvo et al.	[35]
Exosomes from immature DCs plus rapamycin induce tolerance to mouse cardiac allografts	Li et al.	[36]
Clinical studies of tolerogenic DCs
Phase-1 trial of autologous tolerogenic DC therapy in patients with type-1 diabetes	Giannoukakis et al.	[37]
Clinical trials of tolerogenic DC therapy in patients with rheumatoid arthritis	Hilkens and Isaacs	[38]
OneStudy phase-1 trial of autologous tolerogenic DC therapy after kidney transplantation	Moreau et al.	[39]