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Generation of myeloid-derived suppressor cells using prostaglandin E<inf>2</inf>

Obermajer, N and Kalinski, P (2012) Generation of myeloid-derived suppressor cells using prostaglandin E<inf>2</inf>. Transplantation Research, 1 (1).

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Abstract

Myeloid-derived suppressor cells (MDSCs) are natural immunosuppressive cells and endogenous inhibitors of the immune system. We describe a simple and clinically compatible method of generating large numbers of MDSCs using the cultures of peripheral blood-isolated monocytes supplemented with prostaglandin E<inf>2</inf> (PGE<inf>2</inf>). We observed that PGE<inf>2</inf> induces endogenous cyclooxygenase (COX)2 expression in cultured monocytes, blocking their differentiation into CD1a<sup>+</sup> dendritic cells (DCs) and inducing the expression of indoleamine 2,3-dioxygenase 1, IL-4Rα, nitric oxide synthase 2 and IL-10 - typical MDSC-associated suppressive factors. The establishment of a positive feedback loop between PGE<inf>2</inf> and COX2, the key regulator of PGE<inf>2</inf> synthesis, is both necessary and sufficient to promote the development of CD1a<sup>+</sup> DCs to CD14<sup>+</sup>CD33<sup>+</sup>CD34<sup>+</sup> monocytic MDSCs in granulocyte macrophage colony stimulating factor/IL-4-supplemented monocyte cultures, their stability, production of multiple immunosuppressive mediators and cytotoxic T lymphocyte-suppressive function. In addition to PGE<inf>2</inf>, selective E-prostanoid receptor (EP)2- and EP4-agonists, but not EP3/1 agonists, also induce the MDSCs development, suggesting that other activators of the EP2/4- and EP2/4-driven signaling pathway (adenylate cyclase/cAMP/PKA/CREB) may be used to promote the development of suppressive cells. Our observations provide a simple method for generating large numbers of MDSCs for the immunotherapy of autoimmune diseases, chronic inflammatory disorders and transplant rejection. © 2012 Obermajer and Kalinski; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Obermajer, Nnao22@pitt.eduNAO22
Kalinski, Ppak5@pitt.eduPAK5
Centers: Other Centers, Institutes, or Units > Hillman Cancer Center
Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 28 September 2012
Date Type: Publication
Journal or Publication Title: Transplantation Research
Volume: 1
Number: 1
DOI or Unique Handle: 10.1186/2047-1440-1-15
Schools and Programs: School of Medicine > Immunology
School of Medicine > Infectious Diseases and Microbiology
School of Medicine > Surgery
Refereed: Yes
Article Type: Review
Date Deposited: 11 Oct 2016 18:32
Last Modified: 04 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/29825

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