2. Academic Validation
  3. Dendritic cells overcome Cre/Lox induced gene deficiency by siphoning cytosolic material from surrounding cells

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

  • iScience. 2024 Feb 6;27(3):109119. doi: 10.1016/j.isci.2024.109119.
Christopher H Herbst 1,  Aurélie Bouteau 1,  Evelin J Menykő 1,  Zhen Qin 1,  Ervin Gyenge 1,  Qingtai Su 2,  Vincent Cooper 1,  Neil A Mabbott 3,  Botond Z Igyártó 1
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
  • 2 OncoNano Medicine, Inc, Southlake, TX 76092, USA.
  • 3 The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
PMID: 38384841 DOI: 10.1016/j.isci.2024.109119
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.

Keywords

Cell biology; Components of the immune system; Immunology.

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