Dendritic cells overcome Cre/Lox induced gene deficiency by siphoning cytosolic material from surrounding cells

树突状细胞通过从周围细胞吸收胞质物质来克服 Cre/Lox 诱导的基因缺陷。

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

Abstract

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 for lost gene products in cells subjected 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.

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