NDLI: Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with combination of regulatory T cells

Content Provider	Springer Nature : BioMed Central
Author	Park, Min-Jung Baek, Jin-Ah Kim, Se-Young Jung, Kyung-Ah Choi, Jeong Won Park, Sung-Hwan Kwok, Seung‐Ki Cho, Mi-La
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 therapeutic 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 proinflammatory 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.
Related Links	https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-020-02657-6.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14795876
DOI	10.1186/s12967-020-02657-6
Journal	Journal of Translational Medicine
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2020-12-14
Access Restriction	Open
Subject Keyword	Biomedicine Medicine Public Health Myeloid-derived suppressor cells Regulatory T cells Graft-versus-host disease Immune tolerance Cell therapy Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Medicine
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	6.3/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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