Amniotic MSC affect CD8 naive polarization toward SLEC/MPEC subsets by down-modulating IL-12Rβ1 and IL-2Rα signaling pathways

Andrea Papait; Elsa Vertua; Patrizia Bonassi Signoroni; Anna Cargnoni; Marta Magatti; Francesca Romana Stefani; Jacopo Romoli; Antonietta Rosa Silini; Ornella Parolini

doi:10.1016/j.isci.2023.108483

Amniotic MSC affect CD8 naive polarization toward SLEC/MPEC subsets by down-modulating IL-12Rβ1 and IL-2Rα signaling pathways

iScience. 2023 Nov 17;26(12):108483. doi: 10.1016/j.isci.2023.108483. eCollection 2023 Dec 15.

Authors

Affiliations

¹ Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
² Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Rome, Italy.
³ Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy.

Abstract

Mesenchymal stromal cells (MSCs) are known for their immunomodulatory activity. Here, we report that MSCs isolated from the amniotic membrane of human term placenta (hAMSCs) impact CD8 T cell fate through a multifaceted mechanism. We observed that hAMSCs are able to impact the metabolism of naive CD8 lymphocytes by downregulating the phosphorylation of mTOR and AKT, thus blocking cell differentiation. This effect is due to the ability of hAMSCs to reduce the expression of two receptors, IL-12Rβ1 and IL-2RA, resulting in reduced phosphorylation of STAT4 and STAT5. In addition, hAMSCs reduce the expression of two transcriptional factors, Tbet and Eomes, directly involved in early effector cell commitment. Our results unravel an unknown feature of MSCs, offering alternative mechanistic insights into the effects of MSCs for the treatment of diseases characterized by an altered activation of memory subsets, such as autoimmune diseases and graft versus host disease.

Keywords: Cell biology; Components of the immune system; Immunology; Stem cells research.