Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
BMC Immunology
Published in: BMC Immunology 1/2017

Open Access 01-12-2017 | Research article

Forkhead-box transcription factor 1 affects the apoptosis of natural regulatory T cells by controlling Aven expression

Authors: Zhitao Cai, Hong Liu, Xiongfei Wu

Published in: BMC Immunology | Issue 1/2017

Login to get access

Abstract

Background

Regulatory T (Treg) cells play important roles in autoimmune diseases, cancer, and organ transplantation. Forkhead box protein o1 (Foxo1) and IL-7Rα(CD127) are closely related to the homeostasis of Treg cells. However, the mechanism underlying Treg proliferation and activation remains unclear. Here, we evaluated how the over-expression of Foxo1 affects Treg cell proliferation via intracellular signaling. nTreg cells were transfected separately with Foxo1 and Aven small-interfering RNA (siRNA) or over-expression plasmid. The expression of signaling pathway genes and CD127 was confirmed using RT-qPCR and western blot analysis. The expression of cell surface molecules and apoptosis was confirmed by Flow Cytometry 3-(4, 5-Dimethylthiazol-2-yl) 2,5- diphenyltetrazolium bromide for cell proliferation assays.

Results

Foxo1 strengthened the proliferative ability of Treg cells by activating IL-7/CD127 signaling. In addition, Foxo1 suppressed Treg cell apoptosis by regulating Aven expression.

Conclusions

The results in this study indicated that Foxo1 is a positive regulatory factor for the proliferation and activity of Treg cells. Foxo1 might be a potential target for the activation of nTreg cells in vivo and in vitro.
Literature
1.
2.
Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T, Sakaguchi S. Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature. 2007;446(7136):685–9.CrossRefPubMed
3.
Ersvaer E, Liseth K, Skavland J, Gjertsen BT, Bruserud O. Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells. BMC Immunol. 2010;11:38.CrossRefPubMedPubMedCentral
4.
5.
6.
Oleinika K, Nibbs RJ, Graham GJ, Fraser AR. Suppression, subversion and escape: the role of regulatory T cells in cancer progression. Clin Exp Immunol. 2013;171(1):36–45.CrossRefPubMed
7.
Schliesser U, Streitz M, Sawitzki B. Tregs: application for solid-organ transplantation. Curr Opin Organ Transplant. 2012;17(1):34–41.CrossRefPubMed
8.
Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T. Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med. 1985;161(1):72–87.CrossRefPubMed
9.
Waldmann H, Adams E, Fairchild P, Cobbold S. Infectious tolerance and the long-term acceptance of transplanted tissue. Immunol Rev. 2006;212:301–13.CrossRefPubMed
10.
Gorczynski RM. Thymocyte/splenocyte-derived CD4 + CD25 + Treg stimulated by anti-CD200R2 derived dendritic cells suppress mixed leukocyte cultures and skin graft rejection. Transplantation. 2006;81(7):1027–34.CrossRefPubMed
11.
Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4 + CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9(9):1144–50.CrossRefPubMed
12.
Atanackovic D, Cao Y, Luetkens T, Panse J, Faltz C, Arfsten J, Bartels K, Wolschke C, Eiermann T, Zander AR, et al. CD4 + CD25 + FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation. Haematologica. 2008;93(3):423–30.CrossRefPubMed
13.
MacDonald KG, Hoeppli RE, Huang Q, Gillies J, Luciani DS, Orban PC, Broady R, Levings MK. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J Clin Invest. 2016;126(4):1413–24.CrossRefPubMedPubMedCentral
14.
Peffault de Latour R, Dujardin HC, Mishellany F, Burlen-Defranoux O, Zuber J, Marques R, Di Santo J, Cumano A, Vieira P, Bandeira A. Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7. Blood. 2006;108(7):2300–6.CrossRefPubMed
15.
Mazzucchelli R, Hixon JA, Spolski R, Chen X, Li WQ, Hall VL, Willette-Brown J, Hurwitz AA, Leonard WJ, Durum SK. Development of regulatory T cells requires IL-7Ralpha stimulation by IL-7 or TSLP. Blood. 2008;112(8):3283–92.CrossRefPubMedPubMedCentral
16.
17.
Ouyang W, Liao W, Luo CT, Yin N, Huse M, Kim MV, Peng M, Chan P, Ma Q, Mo Y, et al. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 2012;491(7425):554–9.CrossRefPubMedPubMedCentral
18.
Hedrick SM, Hess Michelini R, Doedens AL, Goldrath AW, Stone EL. FOXO transcription factors throughout T cell biology. Nat Rev Immunol. 2012;12(9):649–61.CrossRefPubMed
19.
Ouyang W, Beckett O, Flavell RA, Li MO. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity. 2009;30(3):358–71.CrossRefPubMedPubMedCentral
20.
Melzer IM, Fernandez SB, Bosser S, Lohrig K, Lewandrowski U, Wolters D, Kehrloesser S, Brezniceanu ML, Theos AC, Irusta PM, et al. The Apaf-1-binding protein Aven is cleaved by Cathepsin D to unleash its anti-apoptotic potential. Cell Death Differ. 2012;19(9):1435–45.CrossRefPubMedPubMedCentral
21.
Nakae J, Kitamura T, Silver DL, Accili D. The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest. 2001;108(9):1359–67.CrossRefPubMedPubMedCentral
22.
Lund JM, Hsing L, Pham TT, Rudensky AY. Coordination of early protective immunity to viral infection by regulatory T cells. Science. 2008;320(5880):1220–4.CrossRefPubMedPubMedCentral
23.
Scott-Browne JP, Shafiani S, Tucker-Heard G, Ishida-Tsubota K, Fontenot JD, Rudensky AY, Bevan MJ, Urdahl KB. Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J Exp Med. 2007;204(9):2159–69.CrossRefPubMedPubMedCentral
24.
Yates J, Rovis F, Mitchell P, Afzali B, Tsang J, Garin M, Lechler RI, Lombardi G, Garden OA. The maintenance of human CD4+ CD25+ regulatory T cell function: IL-2, IL-4, IL-7 and IL-15 preserve optimal suppressive potency in vitro. Int Immunol. 2007;19(6):785–99.CrossRefPubMed
25.
26.
Amorosi S, D’Armiento M, Calcagno G, Russo I, Adriani M, Christiano AM, Weiner L, Brissette JL, Pignata C. FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus. Clin Genet. 2008;73(4):380–4.CrossRefPubMed
27.
Pignata C, Fusco A, Amorosi S. Human clinical phenotype associated with FOXN1 mutations. Adv Exp Med Biol. 2009;665:195–206.CrossRefPubMed
28.
Carrette F, Fabre S, Bismuth G. FOXO1, T-cell trafficking and immune responses. Adv Exp Med Biol. 2009;665:3–16.CrossRefPubMed
29.
Kerdiles YM, Beisner DR, Tinoco R, Dejean AS, Castrillon DH, DePinho RA, Hedrick SM. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat Immunol. 2009;10(2):176–84.CrossRefPubMedPubMedCentral
30.
Chau BN, Cheng EH, Kerr DA, Hardwick JM. Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1. Mol Cell. 2000;6(1):31–40.CrossRefPubMed
Metadata
Title
Forkhead-box transcription factor 1 affects the apoptosis of natural regulatory T cells by controlling Aven expression
Authors
Zhitao Cai
Hong Liu
Xiongfei Wu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2017
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-017-0198-8

Other articles of this Issue 1/2017

BMC Immunology 1/2017 Go to the issue

Research article

Lipopolysaccharide mediates immuno-pathological alterations in young chicken liver through TLR4 signaling

Research article

Effect of cryopreservation on delineation of immune cell subpopulations in tumor specimens as determined by multiparametric single cell mass cytometry analysis

Research article

The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP

Research article

Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies?

Research article

Monocyte differentiation and macrophage priming are regulated differentially by pentraxins and their ligands

Research article

Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits