Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes

Guibin Chen, Francesca Calcaterra, Yuchi Ma, Xianfeng Ping, Elena Pontarini, Dan Yang, Ferdinando Oriolo, Zhen Yu, Assunta Cancellara, Joanna Mikulak, Yuting Huang, Silvia Della Bella, Yangtengyu Liu, Leslie G. Biesecker, Rebecca L. Harper, Clifton L. Dalgard, Manfred Boehm*, Domenico Mavilio

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The C-C chemokine receptor type 5 (CCR5) expressed on immune cells supports inflammatory responses by directing cells to the inflammation site. CCR5 is also a major coreceptor for macrophage tropic human immunodeficiency viruses (R5-HIV-1) and its variants can confer protection from HIV infection, making it an ideal candidate to target for therapy. We developed a stepwise protocol that differentiates induced pluripotent stem cells (iPSCs) from individuals homozygous for the CCR5Δ32 variant and healthy volunteers into myeloid lineage induced monocytes (iMono) and macrophages (iMac). By characterizing iMono and iMac against their primary counterparts, we demonstrated that CCR5Δ32 homozygous cells are endowed with similar pluripotent potential for self-renewal and differentiation as iPSC lines generated from non-variant individuals while also showing resistance to HIV infection. In conclusion, these cells are a platform to investigate CCR5 pathophysiology in HIV-positive and negative individuals and to help develop novel therapies.

Original languageEnglish
Article number108331
JournaliScience
Volume26
Issue number11
DOIs
StatePublished - 17 Nov 2023
Externally publishedYes

Keywords

  • Immunology
  • Molecular biology
  • Stem cells research

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