iScience (Sep 2023)

Unveiling the immunomodulatory shift: Epithelial-mesenchymal transition Alters immune mechanisms of amniotic epithelial cells

  • Valeria Di Lollo,
  • Angelo Canciello,
  • Alessia Peserico,
  • Massimiliano Orsini,
  • Valentina Russo,
  • Adrián Cerveró-Varona,
  • Beatrice Dufrusine,
  • Mohammad El Khatib,
  • Valentina Curini,
  • Annunziata Mauro,
  • Paolo Berardinelli,
  • Cathy Tournier,
  • Massimo Ancora,
  • Cesare Cammà,
  • Enrico Dainese,
  • Luana Fiorella Mincarelli,
  • Barbara Barboni

Journal volume & issue
Vol. 26, no. 9
p. 107582

Abstract

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Summary: Epithelial-mesenchymal transition (EMT) changes cell phenotype by affecting immune properties of amniotic epithelial cells (AECs). The present study shows how the response to lipopolysaccharide of cells collected pre- (eAECs) and post-EMT (mAECs) induces changes in their transcriptomics profile. In fact, eAECs mainly upregulate genes involved in antigen-presenting response, whereas mAECs over-express soluble inflammatory mediator transcripts. Consistently, network analysis identifies CIITA and Nrf2 as main drivers of eAECs and mAECs immune response, respectively. As a consequence, the depletion of CIITA and Nrf2 impairs the ability of eAECs and mAECs to inhibit lymphocyte proliferation or macrophage-dependent IL-6 release, thus confirming their involvement in regulating immune response. Deciphering the mechanisms controlling the immune function of AECs pre- and post-EMT represents a step forward in understanding key physiological events wherein these cells are involved (pregnancy and labor). Moreover, controlling the immunomodulatory properties of eAECs and mAECs may be essential in developing potential strategies for regenerative medicine applications.

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