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

doi:10.1016/j.isci.2023.107582

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

iScience. 2023 Aug 9;26(9):107582. doi: 10.1016/j.isci.2023.107582. eCollection 2023 Sep 15.

Authors

Valeria Di Lollo¹, Angelo Canciello², Alessia Peserico², Massimiliano Orsini^{1

3}, Valentina Russo², Adrián Cerveró-Varona², Beatrice Dufrusine², Mohammad El Khatib², Valentina Curini¹, Annunziata Mauro², Paolo Berardinelli², Cathy Tournier⁴, Massimo Ancora¹, Cesare Cammà¹, Enrico Dainese², Luana Fiorella Mincarelli¹, Barbara Barboni²

Affiliations

¹ National Reference Center for Whole Genome Sequencing of Microbial Pathogens: Database and Bioinformatic Analysis, Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise, Campo Boario, 64100 Teramo, Italy.
² Department of Biosciences and Technology for Food, Agriculture and Environment, University of Teramo, Via Balzarini 1, 64100 Teramo, Italy.
³ Istituto Zooprofilattico Sperimentale delle Venezie, Department of Microbiology, Viale dell'Università 10, 35020 Legnaro (PD), Italy.
⁴ Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK.

Abstract

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.

Keywords: Cell biology; Immunology; Stem cells research; Transcriptomics.