Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 17, Issue 1, Pages 95-107Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41423-019-0218-0
Keywords
Dendritic cells; IL-10; T regulatory type 1 (Tr1) cells; Tolerance
Categories
Funding
- Italian Telethon Foundation [TGT17G01]
- Italian Association for Cancer Research [IG-18540]
- COST Action A-FAACT [BM1305]
- COST Action Mye-EUNITER [BM1404]
- EU
- NSF [DGE - 1147470]
- AIRC
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Tolerogenic dendritic cells (DCs) are key players in maintaining immunological homeostasis, dampening immune responses, and promoting tolerance. DC-10, a tolerogenic population of human IL-10-producing DCs characterized by the expression of HLA-G and ILT4, play a pivotal role in promoting tolerance via T regulatory type 1 (Tr1) cells. Thus far, the absence of markers that uniquely identify DC-10 has limited in vivo studies. By in vitro gene expression profiling of differentiated human DCs, we identified CD141 and CD163 as surface markers for DC-10. The coexpression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of DC-10 from the peripheral blood. CD14(+)CD16(+)CD141(+)CD163(+) cells isolated from the peripheral blood of healthy subjects (ex vivo DC-10) produced spontaneously and upon activation of IL-10 and limited levels of IL-12. Moreover, in vitro stimulation of allogeneic naive CD4(+) T cells with ex vivo DC-10 induced the differentiation of alloantigen-specific CD49b(+)LAG-3(+) Tr1 cells. Finally, ex vivo DC-10 and in vitro generated DC-10 exhibited a similar transcriptional profile, which are characterized by an anti-inflammatory and pro-tolerogenic signature. These results provide new insights into the phenotype and molecular signature of DC-10 and highlight the tolerogenic properties of circulating DC-10. These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.
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