Dendritic Cells Overcome Cre/Lox Induced Gene Deficiency by Siphoning Cytosolic Material from Surrounding Cells

Christopher H. Herbst, Aurélie Bouteau, Evelin J. Menykő, Zhen Qin, Ervin Gyenge, Qingtai Su, Vincent Cooper, Neil Mabbott, Botond Z. Igyártó*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

In a previous report, keratinocytes were shown to share their gene expression profile with surrounding Langerhans cells (LCs), influencing LC biology. Here, we investigated whether transferred material could substitute gene products in cells subject to Cre/Lox conditional gene deletion. We found that in human Langerin Cre mice, epidermal LCs and CD11b+CD103+ mesenteric DCs overcome gene deletion if the deleted gene was expressed by neighboring cells. The mechanism of material transfer differed from traditional antigen uptake routes, relying on calcium and PI3K, being susceptible to polyguanylic acid inhibition, and remaining unaffected by inflammation. Termed intracellular monitoring, this process was specific to DCs, occurring in all murine DC subsets tested and human monocyte-derived DCs. The transferred material was presented on MHC-I and MHC-II, suggesting a role in regulating immune responses.
Original languageEnglish
Article number109119
Pages (from-to)1-24
Number of pages24
JournaliScience
Volume27
Issue number3
Early online date6 Feb 2024
DOIs
Publication statusPublished - 15 Mar 2024

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