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Dendritic cells modulate c-kit expression on the edge between activation and death

Simonetti, S; Barroeta Seijas, A; Natalini, A; Vitale, S; Runci, D; Soriani, A; Di Virgilio, A; ... Di Rosa, F; + view all (2019) Dendritic cells modulate c-kit expression on the edge between activation and death. European Journal of Immunology , 49 (4) pp. 534-545. 10.1002/eji.201847683. Green open access

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Abstract

Dendritic cells (DCs) are key players in immunity and tolerance. Some DCs express c‐kit, the receptor for stem cell factor (SCF), nevertheless c‐kit functional role and the regulation of its expression in DCs are incompletely defined. We recently demonstrated that autocrine SCF sustains a pro‐survival circuit, and that SCF increases phospho‐AKT in c‐kit+ mouse bone marrow‐derived DCs (BMdDCs). Herein we observed that CpG and PolyI:C, two stimuli mimicking bacterial and viral nucleic acids respectively, strongly inhibited c‐kit expression by BMdDCs and spleen DCs in vitro and in vivo. Experiments in IFNARI−/− mice showed that IFN‐I pathway was required for c‐kit down‐regulation in cDC1s, but only partially supported it in cDC2s. Furthermore, CpG and PolyI:C strongly inhibited c‐kit mRNA expression. In agreement with the reduced c‐kit levels, SCF pro‐survival activity was impaired. Thus in the presence of exogenously provided SCF, either PolyI:C or CpG induced spleen DC death in 2 days, while at earlier times IL‐6 and IL‐12 production were slightly increased. In contrast, SCF improved survival of unstimulated spleen DCs expressing high c‐kit levels. Our studies suggest that c‐kit down‐modulation is a previously neglected component of DC response to CpG and PolyI:C, regulating DC survival and ultimately tuning immune response.

Type: Article
Title: Dendritic cells modulate c-kit expression on the edge between activation and death
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/eji.201847683
Publisher version: https://doi.org/10.1002/eji.201847683
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: conventional dendritic cell subsets, dendritic cell survival, CpG, PolyI:C, Stem cell factor
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10072112
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