Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with com
- PDF / 11,096,708 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 51 Downloads / 151 Views
Journal of Translational Medicine Open Access
RESEARCH
Myeloid‑derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with combination of regulatory T cells Min‑Jung Park1, Jin‑Ah Baek1, Se‑Young Kim1, Kyung‑Ah Jung1, Jeong Won Choi1, Sung‑Hwan Park1,2, Seung‐ Ki Kwok1,2 and Mi‑La Cho1*
Abstract Background: Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and promoting immune tolerance in models of autoimmunity and transplantation. Regulatory T cells (Tregs) exert thera‑ peutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting. Methods: We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for a murine aGVHD model following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysis. Results: We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice and human system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD mouse model by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proin‑ flammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3 + Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset. Conclusions: Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD. Keywords: Myeloid-derived suppressor cells, Regulatory T cells, Graft-versus-host disease, Immune tolerance, Cell therapy
*Correspondence: [email protected] 1 The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo‑dong, Seocho‑gu, Seoul 137‑040, South Korea Full list of author information is available at the end of the article
Background Graft-versus-host disease (GVHD) is the major complications after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) [1, 2]. During GVHD, allogenic T cells are differentiated into effector lineages and
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appro
Data Loading...
