Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP

Oncotarget

Volumn 6, Issue 24, 2015, Pages 20026-20036

  Elkord, Eyad ^a,b,c   Al Samid, May Abd ^a,b   Chaudhary, Belal ^b,d  

^a UNITED ARAB EMIRATES UNIVERSITY   (United Arab Emirates)

^b UNIVERSITY OF SALFORD   (United Kingdom)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

FoxP3; GARP LAP; Helios; Immune response; Immunity; Immunology and microbiology section; Regulatory T cells

Indexed keywords

BIOLOGICAL MARKER; GAMMA INTERFERON; GLYCOPROTEIN A REPETITIONS PREDOMINANT; HELIOS PROTEIN; INTERLEUKIN 10; LATENCY ASSOCIATED PEPTIDE; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN; CCAAT ENHANCER BINDING PROTEIN BETA; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN; IKAROS TRANSCRIPTION FACTOR; IKZF2 PROTEIN, HUMAN; IL10 PROTEIN, HUMAN; LRRC32 PROTEIN, HUMAN; MEMBRANE PROTEIN;

ARTICLE; BINDING AFFINITY; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; CYTOKINE RELEASE; EFFECTOR CELL; HUMAN; HUMAN CELL; IMMUNOSUPPRESSIVE TREATMENT; IN VITRO STUDY; LYMPHOCYTE ACTIVATION; LYMPHOCYTE PROLIFERATION; LYMPHOCYTE SUBPOPULATION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REGULATORY T LYMPHOCYTE; STEADY STATE; T LYMPHOCYTE ACTIVATION; UPREGULATION; BIOSYNTHESIS; BLOOD; CELL CULTURE; IMMUNOLOGY;

CCAAT-ENHANCER-BINDING PROTEIN-BETA; CELLS, CULTURED; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IKAROS TRANSCRIPTION FACTOR; INTERLEUKIN-10; LYMPHOCYTE ACTIVATION; MEMBRANE PROTEINS; T-LYMPHOCYTES, REGULATORY;

EID: 84940171692     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.4771     Document Type: Article

References (50)

1. Elkord E, Alcantar-Orozco EM, Dovedi SJ, Tran DQ, Hawkins RE, Gilham DE. T regulatory cells in cancer: recent advances and therapeutic potential. Expert Opin Biol Ther. 2010; 10:1573-1586.
2. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010; 10:490-500.
3. Tang Q, Bluestone JA. Regulatory T-cell therapy in transplantation: moving to the clinic. Cold Spring Harb Perspect Med. 2013; 3.
4. von Boehmer H, Daniel C. Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer. Nat Rev Drug Discov. 2013; 12:51-63.
5. Chaudhary B, Abd Al Samid M, al-Ramadi BK, Elkord E. Phenotypic alterations, clinical impact and therapeutic potential of regulatory T cells in cancer. Expert Opin Biol Ther. 2014; 14:931-945.
6. Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, Levings MK. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev. 2006; 212:28-50.
7. Weiner HL, da Cunha AP, Quintana F, Wu H. Oral tolerance. Immunol Rev. 2011; 241:241-259.
8. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003; 299:1057-1061.
9. Chaudhary B, Khaled YS, Ammori BJ, Elkord E. Neuropilin 1: function and therapeutic potential in cancer. Cancer Immunol Immunother. 2014; 63:81-99.
10. E Xq, Meng HX, Cao Y, Zhang SQ, Bi ZG, Yamakawa M. Distribution of regulatory T cells and interaction with dendritic cells in the synovium of rheumatoid arthritis. Scand J Rheumatol. 2012; 41:413-420.
11. Pillai V, Ortega SB, Wang CK, Karandikar NJ. Transient regulatory T-cells: a state attained by all activated human T-cells. Clin Immunol. 2007; 123:18-29.
12. Miyao T, Floess S, Setoguchi R, Luche H, Fehling HJ, Waldmann H, Huehn J, Hori S. Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity. 2012; 36:262-275.
13. Tran DQ, Andersson J, Wang R, Ramsey H, Unutmaz D, Shevach EM. GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009; 106:13445-13450.
14. Stockis J, Colau D, Coulie PG, Lucas S. Membrane protein GARP is a receptor for latent TGF-beta on the surface of activated human Treg. Eur J Immunol. 2009; 39:3315-3322.
15. Wang R, Kozhaya L, Mercer F, Khaitan A, Fujii H, Unutmaz D. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2009; 106:13439-13444.
16. Probst-Kepper M, Geffers R, Kroger A, Viegas N, Erck C, Hecht HJ, Lunsdorf H, Roubin R, Moharregh-Khiabani D, Wagner K, Ocklenburg F, Jeron A, Garritsen H, Arstila TP, Kekalainen E, Balling R, et al. GARP: a key receptor controlling FOXP3 in human regulatory T cells. Journal of cellular and molecular medicine. 2009; 13:3343-3357.
17. Probst-Kepper M, Buer J. FOXP3 and GARP (LRRC32): the master and its minion. Biol Direct. 2010; 5:8.
18. Probst-Kepper M, Kroger A, Garritsen HS, Buer J. Perspectives on Regulatory T Cell Therapies. Transfus Med Hemother. 2009; 36:302-308.
19. Wang R, Wan Q, Kozhaya L, Fujii H, Unutmaz D. Identification of a regulatory T cell specific cell surface molecule that mediates suppressive signals and induces Foxp3 expression. PLoS One. 2008; 3:e2705.
20. Hahn SA, Stahl HF, Becker C, Correll A, Schneider FJ, Tuettenberg A, Jonuleit H. Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4(+) T cells. Blood. 2013; 122:1182-1191.
21. Gandhi R, Anderson DE, Weiner HL. Cutting Edge: Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-beta-dependent manner. J Immunol. 2007; 178:4017-4021.
22. Tran DQ, Andersson J, Hardwick D, Bebris L, Illei GG, Shevach EM. Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures. Blood. 2009; 113:5125-5133.
23. Gandhi R, Farez MF, Wang Y, Kozoriz D, Quintana FJ, Weiner HL. Cutting edge: human latency-associated peptide+ T cells: a novel regulatory T cell subset. J Immunol. 2010; 184:4620-4624.
24. Sun J, Tang DN, Fu T, Sharma P. Identification of human regulatory T cells in the setting of T-cell activation and anti-CTLA-4 immunotherapy on the basis of expression of latency-associated peptide. Cancer Discov. 2012; 2:122-130.
25. Sugimoto N, Oida T, Hirota K, Nakamura K, Nomura T, Uchiyama T, Sakaguchi S. Foxp3-dependent and-independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int Immunol. 2006; 18:1197-1209.
26. Akimova T, Beier UH, Wang L, Levine MH, Hancock WW. Helios expression is a marker of T cell activation and proliferation. PLoS One. 2011; 6:e24226.
27. Baine I, Basu S, Ames R, Sellers RS, Macian F. Helios induces epigenetic silencing of IL2 gene expression in regulatory T cells. J Immunol. 2013; 190:1008-1016.
28. Ross EM, Bourges D, Hogan TV, Gleeson PA, van Driel IR. Helios defines T cells being driven to tolerance in the periphery and thymus. Eur J Immunol. 2014; 44:2048-2058.
29. Sugita K, Hanakawa S, Honda T, Kondoh G, Miyachi Y, Kabashima K, Nomura T. Generation of Helios reporter mice and an evaluation of the suppressive capacity of Helios regulatory T cells in vitro. Exp Dermatol. 2015; 24:554-6.
30. Getnet D, Grosso JF, Goldberg MV, Harris TJ, Yen HR, Bruno TC, Durham NM, Hipkiss EL, Pyle KJ, Wada S, Pan F, Pardoll DM, Drake CG. A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells. Mol Immunol. 2010; 47:1595-1600.
31. Zabransky DJ, Nirschl CJ, Durham NM, Park BV, Ceccato CM, Bruno TC, Tam AJ, Getnet D, Drake CG. Phenotypic and functional properties of Helios+ regulatory T cells. PLoS One. 2012; 7:e34547.
32. Himmel ME, MacDonald KG, Garcia RV, Steiner TS, Levings MK. Helios+ and Helios-cells coexist within the natural FOXP3+ T regulatory cell subset in humans. J Immunol. 2013; 190:2001-2008.
33. Raffin C, Pignon P, Celse C, Debien E, Valmori D, Ayyoub M. Human memory Helios-FOXP3+ regulatory T cells (Tregs) encompass induced Tregs that express Aiolos and respond to IL-1beta by downregulating their suppressor functions. J Immunol. 2013; 191:4619-4627.
34. Elkord E, Al-Ramadi BK. Helios expression in FoxP3(+) T regulatory cells. Expert Opin Biol Ther. 2012; 12:1423-1425.
35. Elkord E, Sharma S, Burt DJ, Hawkins RE. Expanded subpopulation of FoxP3+ T regulatory cells in renal cell carcinoma co-express Helios, indicating they could be derived from natural but not induced Tregs. Clin Immunol. 2011; 140:218-222.
36. Scurr M, Ladell K, Besneux M, Christian A, Hockey T, Smart K, Bridgeman H, Hargest R, Phillips S, Davies M, Price D, Gallimore A, Godkin A. Highly prevalent colorectal cancer-infiltrating LAP(+) Foxp3(-) T cells exhibit more potent immunosuppressive activity than Foxp3(+) regulatory T cells. Mucosal Immunol. 2014; 7:428-439.
37. Wainwright DA, Sengupta S, Han Y, Lesniak MS. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro Oncol. 2011; 13:1308-1323.
38. Zhu ZF, Meng K, Zhong YC, Qi L, Mao XB, Yu KW, Zhang W, Zhu PF, Ren ZP, Wu BW, Ji QW, Wang X, Zeng QT. Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study. PLoS One. 2014; 9:e88775.
39. Bin Dhuban K, d'Hennezel E, Nashi E, Bar-Or A, Rieder S, Shevach EM, Nagata S, Piccirillo CA. Coexpression of TIGIT and FCRL3 identifies Helios+ human memory regulatory T cells. J Immunol. 2015; 194:3687-3696.
40. Kim YC, Bhairavabhotla R, Yoon J, Golding A, Thornton AM, Tran DQ, Shevach EM. Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion. Blood. 2012; 119:2810-2818.
41. Alexander T, Sattler A, Templin L, Kohler S, Gross C, Meisel A, Sawitzki B, Burmester GR, Arnold R, Radbruch A, Thiel A, Hiepe F. Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus. Ann Rheum Dis. 2013; 72:1549-1558.
42. Golding A, Hasni S, Illei G, Shevach EM. The percentage of FoxP3+Helios+ Treg cells correlates positively with disease activity in systemic lupus erythematosus. Arthritis Rheum. 2013; 65:2898-2906.
43. Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity. 2009; 30:636-645.
44. Serre K, Benezech C, Desanti G, Bobat S, Toellner KM, Bird R, Chan S, Kastner P, Cunningham AF, Maclennan IC, Mohr E. Helios is associated with CD4 T cells differentiating to T helper 2 and follicular helper T cells in vivo independently of Foxp3 expression. PLoS One. 2011; 6:e20731.
45. Edwards JP, Fujii H, Zhou AX, Creemers J, Unutmaz D, Shevach EM. Regulation of the expression of GARP/latent TGF-beta1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation. J Immunol. 2013; 190:5506-5515.
46. Addey C, White M, Dou L, Coe D, Dyson J, Chai JG. Functional plasticity of antigen-specific regulatory T cells in context of tumor. J Immunol. 2011; 186:4557-4564.
47. Duhen T, Duhen R, Lanzavecchia A, Sallusto F, Campbell DJ. Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells. Blood. 2012; 119:4430-4440.
48. Whiteside TL. Induced regulatory T cells in inhibitory microenvironments created by cancer. Expert Opin Biol Ther. 2014; 14:1411-1425.
49. Takatori H, Kawashima H, Matsuki A, Meguro K, Tanaka S, Iwamoto T, Sanayama Y, Nishikawa N, Tamachi T, Ikeda K, Suto A, Suzuki K, Kagami SI, Hirose K, Kubo M, Hori S, et al. Helios enhances regulatory T cell function in cooperation with Foxp3. Arthritis Rheumatol. 2015; 67:1491-502.
50. Cherai M, Hamel Y, Baillou C, Touil S, Guillot-Delost M, Charlotte F, Kossir L, Simonin G, Maury S, Cohen JL, Lemoine FM. Generation of human alloantigen-specific regulatory T-cells under good manufacturing practice-compliant conditions for cell therapy. Cell Transplant. 2014; Epub ahead of print.