Tolerogenic dendritic cells and their applications in transplantation

Abstract

In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells (tol-DCs) with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various tol-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.

Combination of CD40 Agonism and CSF-1R Blockade Reconditions Tumor-Associated Macrophages and Drives Potent Antitumor Immunity

“…A prominent effect of combination treatment included lower quantities of IL10. IL10 signaling in DCs potently inhibits maturation and antagonizes IL12 production, resulting in poor activation of T cells and increased promotion of Treg differentiation (34,42). Alternatively, we hypothesized that blocking CSF-1 signals may alter the composition of DCs by reducing frequencies of suppressive tolerogenic DCs that rely on this cytokine for development and survival.…”

Eosinophils promote inducible NOS–mediated lung allograft acceptance

“…A group of DCs, described as tolerogenic DCs, can potentiate solid organ acceptance in other models as well (3). The presence of granulocytic cells, however, is generally considered deleterious for successful organ engraftment.…”

The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

“…Tolerogenic DCs may be naïve immature cells or alternatively activated cells that exhibit resistance to maturation even in the presence of an inducing signal. Immature DCs (iDCs) express high levels of CCR1, CCR2, CCR6, CCR5, CCR7, CXCR1, CXCR2, FcγRII, DEC-205, TLRs, PD-L1 molecules and have lower expression of MHC-II and other co-stimulatory molecules such as CD40, CD80, CD86, CD52 and PD-L2 [122–124]. …”

“…Apart from inducing proliferation and activation of naïve and memory B cells, DCs have also been reported to induce regulatory B cell function and induce tolerance [124, 167]. Under inflammatory conditions, cDCs normally produce IL-12 that induces follicular B cells to develop into IL-12 and IFN-γ producing effector cells [168].…”