TY - JOUR
T1 - Amniotic MSC affect CD8 naive polarization toward SLEC/MPEC subsets by down-modulating IL-12Rβ1 and IL-2Rα signaling pathways
AU - Papait, Andrea
AU - Vertua, E.
AU - Signoroni, P. B.
AU - Cargnoni, A.
AU - Magatti, M.
AU - Stefani, F. R.
AU - Romoli, J.
AU - Silini, A. R.
AU - Parolini, Ornella
PY - 2023
Y1 - 2023
N2 - 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-12R beta 1 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.
AB - 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-12R beta 1 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.
KW - Cell biology
KW - Components of the immune system
KW - Immunology
KW - Stem cells research
KW - Cell biology
KW - Components of the immune system
KW - Immunology
KW - Stem cells research
UR - https://publicatt.unicatt.it/handle/10807/262194
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85177813784&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85177813784&origin=inward
U2 - 10.1016/j.isci.2023.108483
DO - 10.1016/j.isci.2023.108483
M3 - Article
SN - 2589-0042
VL - 26
SP - 108483-N/A
JO - iScience
JF - iScience
IS - 12
ER -
