Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

Directed differentiation of regulatory T cells from naive T cells and prevention of their inflammation-mediated instability using small molecules

Wed Nov 30 07:21:53 2022

(2020) Directed differentiation of regulatory T cells from naive T cells and prevention of their inflammation-mediated instability using small molecules. Clinical and Experimental Immunology. p. 17. ISSN 0009-9104

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Abstract

Regulatory T (T-reg) cell therapy is a promising approach for immune tolerance induction in autoimmunity conditions and cell/organ transplantations. Insufficient isolation yields and impurity during downstream processes and T-reg instability after adoptive transfer in inflammatory conditions are major limitations to T-reg therapy, and indicate the importance of seeking a valid, reliable method for de-novo generation of T-regs. In this research, we evaluated T-reg-like cells obtained from different T-reg differentiation protocols in terms of their yield, purity and activity. Differentiation was performed on naive CD4(+) cells and a naive CD4(+)/T-reg co-culture by using three different protocols - ectopic expression of forkhead box protein P3 (E-FoxP3), soluble transforming growth factor beta (S-TGF) and small molecules N-acetyl puromycin and SR1555 (N-Ac/SR). The results showed that a high yield of a homogeneous population of T-reg-like cells could be achieved by the N-Ac/SR method under a T helper type 17 (Th17)-polarizing condition, particularly interleukin (IL)-6 and TGF-beta, when compared with the E-FoxP3 and S-TGF methods. Surprisingly, SR completely inhibited the differentiation of IL-17-producing cells and facilitated T-reg generation in the inflammatory condition and had highly suppressive activity against T cell proliferation without T-reg-specific demethylase region (TSDR) demethylation. For the first time, to our knowledge, we report the generation of efficient, pure T-reg-like cells by using small molecules during in-vitro inflammatory conditions. Our results suggested that the N-Ac/SR method has several advantages for T-reg generation when compared with the other methods, including a higher purity of T-regs, easier procedure, superior suppressive activity during the inflammatory condition and decreased cost.

Item Type: Article
Creators:
CreatorsEmail
Haddadi, M. H.UNSPECIFIED
Negahdari, B.UNSPECIFIED
Hajizadeh-Saffar, E.UNSPECIFIED
Khosravi-Maharlooei, M.UNSPECIFIED
Basiri, M.UNSPECIFIED
Dabiri, H.UNSPECIFIED
Baharvand, H.UNSPECIFIED
Keywords: differentiation of T-reg exogenous FoxP3 N-acetyl puromycin SR1555 T-reg therapy foxp3 expression tgf-beta down-regulation conversion generation il-6 induction tolerance therapy binding Immunology
Divisions:
Page Range: p. 17
Journal or Publication Title: Clinical and Experimental Immunology
Journal Index: ISI
Identification Number: https://doi.org/10.1111/cei.13453
ISSN: 0009-9104
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/2558

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