Mild Hypothermia Provides Treg Stability

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 22

PMID 28931834

Citations 14

Authors

Natalia Marek-Trzonkowska

Karolina Piekarska

Natalia Filipowicz

Arkadiusz Piotrowski

Magdalena Gucwa

Katrin Vogt

Birgit Sawitzki

Janusz Siebert

Piotr Trzonkowski

Affiliations

Soon will be listed here.

Abstract

Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Recent clinical trials confirmed safety and efficacy of Treg treatment of deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. Therefore, multiple research teams have been studding Treg biology in aim to improve their stability in vitro. In the current paper, we demonstrate that mild hypothermia of 33 °C induces robust proliferation of Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro. Tregs expanded at 33 °C have stronger immunosuppressive potential and remarkably anti-inflammatory phenotype demonstrated by the whole transcriptome sequencing. These observations shed new light on impact of temperature on regulation of immune response. We show that just a simple change in temperature can preserve Treg stability, function and accelerate their proliferation, responding to unanswered question- how to preserve Treg stability in vitro.

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References

Steenwinckel V, Louahed J, Lemaire M, Sommereyns C, Warnier G, McKenzie A . IL-9 promotes IL-13-dependent paneth cell hyperplasia and up-regulation of innate immunity mediators in intestinal mucosa. J Immunol. 2009; 182(8):4737-43. DOI: 10.4049/jimmunol.0801941. View

Marek N, Krzystyniak A, Ergenc I, Cochet O, Misawa R, Wang L . Coating human pancreatic islets with CD4(+)CD25(high)CD127(-) regulatory T cells as a novel approach for the local immunoprotection. Ann Surg. 2011; 254(3):512-8. DOI: 10.1097/SLA.0b013e31822c9ca7. View

Ambada G, Ntsama C, Nji N, Ngu L, Sake C, Lissom A . Phenotypic characterization of regulatory T cells from antiretroviral-naive HIV-1-infected people. Immunology. 2017; 151(4):405-416. PMC: 5506422. DOI: 10.1111/imm.12738. View

Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A, Grabowska M, Derkowska I, Juscinska J . Therapy of type 1 diabetes with CD4(+)CD25(high)CD127-regulatory T cells prolongs survival of pancreatic islets - results of one year follow-up. Clin Immunol. 2014; 153(1):23-30. DOI: 10.1016/j.clim.2014.03.016. View

Okamoto K, Iwai Y, Oh-Hora M, Yamamoto M, Morio T, Aoki K . IkappaBzeta regulates T(H)17 development by cooperating with ROR nuclear receptors. Nature. 2010; 464(7293):1381-5. DOI: 10.1038/nature08922. View

Trapnell C, Pachter L, Salzberg S . TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009; 25(9):1105-11. PMC: 2672628. DOI: 10.1093/bioinformatics/btp120. View

Braza F, Dugast E, Panov I, Paul C, Vogt K, Pallier A . Central Role of CD45RA- Foxp3hi Memory Regulatory T Cells in Clinical Kidney Transplantation Tolerance. J Am Soc Nephrol. 2015; 26(8):1795-805. PMC: 4520169. DOI: 10.1681/ASN.2014050480. View

Wang L, Liu Y, Han R, Beier U, Thomas R, Wells A . Mbd2 promotes foxp3 demethylation and T-regulatory-cell function. Mol Cell Biol. 2013; 33(20):4106-15. PMC: 3811679. DOI: 10.1128/MCB.00144-13. View

Grochot-Przeczek A, Dulak J, Jozkowicz A . Haem oxygenase-1: non-canonical roles in physiology and pathology. Clin Sci (Lond). 2011; 122(3):93-103. DOI: 10.1042/CS20110147. View

10.

Zheng G, Qiu G, Ge M, He J, Huang L, Chen P . Human adipose-derived mesenchymal stem cells alleviate obliterative bronchiolitis in a murine model via IDO. Respir Res. 2017; 18(1):119. PMC: 5472885. DOI: 10.1186/s12931-017-0599-5. View

11.

Hanson D . Fever and the immune response. The effects of physiological temperatures on primary murine splenic T-cell responses in vitro. J Immunol. 1993; 151(1):436-48. View

12.

Vignali D, Collison L, Workman C . How regulatory T cells work. Nat Rev Immunol. 2008; 8(7):523-32. PMC: 2665249. DOI: 10.1038/nri2343. View

13.

Marek-Trzonkowska N, Mysliwiec M, Iwaszkiewicz-Grzes D, Gliwinski M, Derkowska I, Zalinska M . Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes. J Transl Med. 2016; 14(1):332. PMC: 5131539. DOI: 10.1186/s12967-016-1090-7. View

14.

Rudra D, Egawa T, Chong M, Treuting P, Littman D, Rudensky A . Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells. Nat Immunol. 2009; 10(11):1170-7. PMC: 2764816. DOI: 10.1038/ni.1795. View

15.

Hoffmann P, Eder R, Boeld T, Doser K, Piseshka B, Andreesen R . Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion. Blood. 2006; 108(13):4260-7. DOI: 10.1182/blood-2006-06-027409. View

16.

Garlanda C, Dinarello C, Mantovani A . The interleukin-1 family: back to the future. Immunity. 2013; 39(6):1003-18. PMC: 3933951. DOI: 10.1016/j.immuni.2013.11.010. View

17.

Brusko T, Wasserfall C, Agarwal A, Kapturczak M, Atkinson M . An integral role for heme oxygenase-1 and carbon monoxide in maintaining peripheral tolerance by CD4+CD25+ regulatory T cells. J Immunol. 2005; 174(9):5181-6. DOI: 10.4049/jimmunol.174.9.5181. View

18.

Belperio J, Dy M, Murray L, Burdick M, Xue Y, Strieter R . The role of the Th2 CC chemokine ligand CCL17 in pulmonary fibrosis. J Immunol. 2004; 173(7):4692-8. DOI: 10.4049/jimmunol.173.7.4692. View

19.

Trapnell C, Hendrickson D, Sauvageau M, Goff L, Rinn J, Pachter L . Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat Biotechnol. 2012; 31(1):46-53. PMC: 3869392. DOI: 10.1038/nbt.2450. View

20.

Martin G, Tremblay M . HLA-DR, ICAM-1, CD40, CD40L, and CD86 are incorporated to a similar degree into clinical human immunodeficiency virus type 1 variants expanded in natural reservoirs such as peripheral blood mononuclear cells and human lymphoid tissue cultured ex vivo. Clin Immunol. 2004; 111(3):275-85. DOI: 10.1016/j.clim.2004.02.004. View