Synergistic production of TNFα and IFNα by human pDCs incubated with IFNλ3 and IL-3

Finotti, Giulia; Tamassia, Nicola; Cassatella, Marco A.

doi:10.1016/j.cyto.2016.08.005

Cited by 11 publications

(15 citation statements)

References 43 publications

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“…This was found to be the case, as we could show that 30 IU/ml IFNλ3 and 20 ng/ml IL-3 induce in pDCs a synergistic production of both IFNα and TNFα ( 59 ). Moreover, endogenously produced TNFα was found to almost completely control the synergistic production of IFNα in IFNλ3 plus IL-3-treated pDCs ( 59 ). Under the same experimental conditions, or in pDCs incubated with IFNλ3 only, endogenously produced IFNα did not drive ISG mRNA expression, unlike its effect in IL-3-treated pDCs.…”

Section: Production Of Cytokines By Pdcs Incubated With Ifnλsmentioning

confidence: 85%

“…Because flow cytometry experiments uncovered that both IFNλ3 and IL-3 increase the levels of surface CD123 and IFNλR1 in human pDCs ( 54 , 59 ), in a subsequent study, we investigated whether IFNλ3 and IL-3 together could promote stronger pDC responses. This was found to be the case, as we could show that 30 IU/ml IFNλ3 and 20 ng/ml IL-3 induce in pDCs a synergistic production of both IFNα and TNFα ( 59 ). Moreover, endogenously produced TNFα was found to almost completely control the synergistic production of IFNα in IFNλ3 plus IL-3-treated pDCs ( 59 ).…”

Section: Production Of Cytokines By Pdcs Incubated With Ifnλsmentioning

confidence: 99%

“…Under the same experimental conditions, or in pDCs incubated with IFNλ3 only, endogenously produced IFNα did not drive ISG mRNA expression, unlike its effect in IL-3-treated pDCs. On the other hand, endogenous TNFα was found to drive ISG mRNA expression in both IFNλ3- and IL-3-stimulated pDCs ( 59 ).…”

Section: Production Of Cytokines By Pdcs Incubated With Ifnλsmentioning

confidence: 99%

“…For example, 2’-5’-oligoadenylate synthetase 1 (OAS1) and IRF7 mRNAs were found as induced in murine pDCs incubated with 100 ng/ml IFNλ2 ( 52 ). In humans, we and others have reported that both IFNλ1 and IFNλ3 induce the mRNA expression of MX dynamin like GTPase 1 (MX1) ( 59 , 60 ), protein kinase R (PKR), interferon induced protein with tetratricopeptide repeats 1 (IFIT1), ISG ubiquitin-like modifier (ISG15), and C-X-C motif chemokine ligand 10 (CXCL10) ( 54 , 55 , 59 ). Our unpublished observations prove that also CXCL9, TLR7, IFIT2, and TNF-related apoptosis inducing ligand (TRAIL) are induced by IFNλ3 in human pDCs.…”

Section: Expression Of Isg Mrnas and Phosphorylation Of Stats In Ifnλmentioning

confidence: 99%

“…All these mRNAs were shown to reach maximal levels after 18 h of incubation of pDCs treated with 30 IU/ml IFNλ1 or IFNλ3 ( 54 ). Experiments conducted in pDCs preincubated in the presence of anti-IFNαR antibodies, and then cultured with IFNλ3 plus IL-3, which, at the 18 h-time point, express and release much higher levels of, respectively, ISG mRNAs and IFNα, than pDCs incubated with IFNλ3 alone ( 59 ), revealed that endogenous IFNα is minimally involved in autocrinally activating ISG mRNA expression ( 59 ). Consistently, and even though IFNα is typically considered more potent than IFNλ in inducing ISG gene expression, we observed that equivalent concentrations of IFNλ3 and IFNα (e.g., 30 IU/ml) induce, in human pDCs, comparable levels of STAT1 and STAT2 phosphorylation and ISG15, IFIT1, and MX1 transcripts (our unpublished observations).…”

Section: Expression Of Isg Mrnas and Phosphorylation Of Stats In Ifnλmentioning

confidence: 99%

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Interferon-λs and Plasmacytoid Dendritic Cells: A Close Relationship

2017

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Interferon lambdas (IFNλs) are recently discovered cytokines acting not only at the first line of defense against viral infections but also at the mucosal barriers. In fact, a peculiar feature of the IFNλ system is the restricted expression of the functional IFNλR, which is known to be limited to epithelial cells and discrete leukocyte subsets, including the plasmacytoid dendritic cells (pDCs). In the latter case, current data, discussed in this minireview, indicate that IFNλs positively regulate various pDC functions, including pDC expression of interferon-dependent gene (ISG) mRNAs, production of cytokines, survival, and phenotype. Although the knowledge of the effects on pDCs by IFNλs is still incomplete, we speculate that the peculiar pDC responsiveness to IFNλs provide unique advantages for these innate immune cells, not only for viral infections but also during autoimmune disorders and/or tumors, in which pDC involvement and activation variably contribute to their pathogenesis.

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Section: Production Of Cytokines By Pdcs Incubated With Ifnλsmentioning

confidence: 85%