Tonsil‐derived mesenchymal stem cells (T‐MSCs) prevent Th17‐mediated autoimmune response via regulation of the programmed death‐1/programmed death ligand‐1 (PD‐1/PD‐L1) pathway

Abstract

Our knowledge of the immunomodulatory role of mesenchymal stem cells (MSCs) in both the innate and adaptive immune systems has dramatically expanded, providing great promise for treating various autoimmune diseases. However, the contribution of MSCs to Th17-dominant immune disease, such as psoriasis and its underlying mechanism remains elusive. In this study, we demonstrated that human palatine tonsil-derived MSCs (T-MSCs) constitutively express both the membrane-bound and soluble forms of programmed death-ligand 1 (PD-L1), which enables T-MSCs to be distinguished from MSCs originating from other organs (i.e. bone marrow or adipose tissue). We also found that T-MSC-derived PD-L1 effectively represses Th17 differentiation via both cell-to-cell contact and a paracrine effect. Further, T-MSCs increase programmed death-1 (PD-1) expression on T-cells by secreting IFN-β, which may enhance engagement with PD-L1. Finally, transplantation of T-MSCs into imiquimod-induced psoriatic skin inflammation in mice significantly abrogated disease symptoms, mainly by blunting the Th17 response in a PD-L1-dependent manner. This study suggests that T-MSCs might be a promising cell source to treat autoimmune diseases such as psoriasis, via its unique immunoregulatory features. Copyright © 2017 John Wiley & Sons, Ltd.

Conditioned Medium from Human Tonsil-Derived Mesenchymal Stem Cells Enhances Bone Marrow Engraftment via Endothelial Cell Restoration by Pleiotrophin

“…MSCs produce cytokines and growth factors that contribute to recovery from injury by promoting cell proliferation, inhibiting apoptosis, regulating immune responses, and activating endogenous stem cells. Our research group has been using human palatine tonsil as a novel supply of MSCs, and the therapeutic effects of T-MSCs have been investigated in various mouse models of disease including psoriasis [17], BM ablation [18], osteoporosis [19], and liver cirrhosis [31]. Here, we demonstrate that T-MSC paracrine factors enhance BMT effectiveness and CM treatment alone could elicit these effects without the cells.…”

“…Previously, we demonstrated that human palatine tonsil-derived MSCs (T-MSCs) show tissue regenerative and immunomodulatory effects [15][16][17]. In addition, T-MSC infusion in allogeneic BM transplantation (BMT) and senile osteoporosis mouse models improved BM reconstitution [18,19].…”

The Supernatant of Tonsil-Derived Mesenchymal Stem Cell Has Antiallergic Effects in Allergic Rhinitis Mouse Model

“…Recently, palatine tonsil tissue was also identified as a source of MSCs and tonsil-derived MSCs (T-MSCs) showed abundant expression of immunomodulatory proteins, compared with MSCs derived from the bone marrow and adipose tissue [15,16]. Moreover, studies for T-MSCs described an immunomodulatory effect on degenerative or inflammatory diseases [17][18][19][20]. Our previous study also demonstrated an immunomodulatory effect of T-MSCs in a mouse model of allergic rhinitis [21].…”

Application of Tonsil-Derived Mesenchymal Stem Cells in Tissue Regeneration: Concise Review

“…Some of these distinctive markers include CD106 (VCAM‐1) and CD274 (PD‐L1), and have functions in adhesion and migration as well as immunomodulation . In fact, there are numerous studies describing the immunomodulatory properties of TMSCs, most of which are involved in the general downregulation of inflammatory responses .…”

“…PD‐L1 of TMSCs prevents the differentiation of Th17, which is important for the inflammatory response of neutrophils and inflammatory disease . TMSCs can also hinder dendritic cell (DC) maturation and CD4+ T‐cell differentiation , while increasing IL‐10‐producing regulatory B‐cells to downregulate the inflammatory response .…”