The IL-6 signaling pathway contributes critically to the immunomodulatory mechanism of human decidua-derived mesenchymal stromal cells

Hyemin Na; Keon-Il Im; Nayoun Kim; Junseok Lee; Sojin Gil; Gi-June Min; Seok-Goo Cho

doi:10.1016/j.isci.2024.109783

The IL-6 signaling pathway contributes critically to the immunomodulatory mechanism of human decidua-derived mesenchymal stromal cells

iScience. 2024 Apr 18;27(5):109783. doi: 10.1016/j.isci.2024.109783. eCollection 2024 May 17.

Authors

Hyemin Na^{1

2}, Keon-Il Im¹, Nayoun Kim¹, Junseok Lee^{1

2}, Sojin Gil^{1

2}, Gi-June Min^{1

3}, Seok-Goo Cho^{1

2

3}

Affiliations

¹ Institute for Translational Research and Molecular Imaging, The Catholic University of Korea, Seoul, Republic of Korea.
² Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
³ Department of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Abstract

Human bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been proposed as a treatment for graft-versus-host disease (GVHD), which is a major complication following allogeneic hematopoietic cell transplantation. However, clinical trials have not yielded good results, and human decidua-derived mesenchymal stromal cells (DSCs) have been proposed as an alternative. In addition, the mechanism by which DSCs exert their immunomodulatory effects is still unknown. We found that knockdown of IL-6 in DSCs reduced the expression of PD-L1 and PD-L2, which are known as classical immune checkpoint inhibitors. Expression of PD-L1 and PD-L2 was restored by adding recombinant IL-6 to the DSCs. When DSCs and IL-6-knockdown DSCs were administered as treatment in a murine GVHD model, the group receiving IL-6-knockdown DSCs had significantly higher mortality and clinical scores compared to the group receiving DSCs. Taken together, these data suggest that the IL-6 signaling pathway is a crucial contributor to the immunosuppressive capacity of DSCs.

Keywords: Health sciences; Immunology; Stem cells research.