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Comi, M; Avancini, D; de Sio, FS; Villa, M; Uyeda, MJ; Floris, M; Tomasoni, D; Bulfone, A; Roncarolo, MG; Gregori, S.
Coexpression of CD163 and CD141 identifies human circulating IL-10-producing dendritic cells (DC-10)
CELL MOL IMMUNOL. 2020; 17(1): 95-107. Doi: 10.1038/s41423-019-0218-0 [OPEN ACCESS]
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Co-authors Med Uni Graz: Villa Matteo
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Abstract:: 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.
Find related publications in this database (Keywords): Dendritic cells; IL-10; T regulatory type 1 (Tr1) cells; Tolerance