Th17/Treg Ratio in Human Graft-versus-host Disease

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2010 May 21

PMID 20484086

Citations 56

Authors

Philippe Ratajczak

Anne Janin

Regis Peffault de Latour

Christophe Leboeuf

Allison Desveaux

Keyvan Keyvanfar

Marie Robin

Emmanuel Clave

Corine Douay

Anne Quinquenel

Claire Pichereau

Philippe Bertheau

Jean Yves Mary

Gerard Socie

Affiliations

Soon will be listed here.

Abstract

Th17 cells have never been explored in human graft-versus-host disease (GVHD). We studied the correlation between the presence of Th17 cells with histologic and clinical parameters. We first analyzed a cohort of 40 patients with GVHD of the gastrointestinal tract. Tumor necrosis factor (TNF), TNF receptors, and Fas expression, and apoptotic cells, CD4(+)IL-17(+) cells (Th17), and CD4(+)Foxp3(+) cells (Treg) were quantified. A Th17/Treg ratio less than 1 correlated both with the clinical diagnosis (P < .001) and more than 2 pathologic grades (P < .001). A Th17/Treg ratio less than 1 also correlated with the intensity of apoptosis of epithelial cells (P = .03), Fas expression in the cellular infiltrate (P = .003), TNF, and TNF receptor expression (P < .001). We then assessed Th17/Treg ratio in 2 other independent cohorts; a second cohort of 30 patients and confirmed that Th17/Treg ratio less than 1 correlated with the pathologic grade of GI GVHD. Finally, 15 patients with skin GVHD and 11 patients with skin rash but without pathologic GVHD were studied. Results in this third cohort of patients with skin disease confirmed those found in patients with GI GVHD. These analyses in 96 patients suggest that Th17/Treg ratio could be a sensitive and specific pathologic in situ biomarker of GVHD.

Citing Articles

Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice.

Ehx G, Ritacco C, Baron F Biomark Res. 2024; 12(1):139.

PMID: 39543777 PMC: 11566168. DOI: 10.1186/s40364-024-00684-9.

Prediction of Th17/Treg cell balance on length of stay in intensive care units of patients with sepsis.

Wu Y, Wu G, Li M, Chang Y, Yu M, Meng Y J Intensive Med. 2024; 4(2):240-246.

PMID: 38681793 PMC: 11043633. DOI: 10.1016/j.jointm.2023.09.005.

Progress in medical therapy in aplastic anemia: why it took so long?.

Scheinberg P Int J Hematol. 2024; 119(3):248-254.

PMID: 38403842 DOI: 10.1007/s12185-024-03713-3.

Microbes little helpers and suppliers for therapeutic asthma approaches.

Reuter S, Raspe J, Taube C Respir Res. 2024; 25(1):29.

PMID: 38218816 PMC: 10787474. DOI: 10.1186/s12931-023-02660-7.

A Species-Specific Anti-Human P2X7 Monoclonal Antibody Reduces Graft-versus-Host Disease in Humanised Mice.

Elhage A, Cuthbertson P, Sligar C, Watson D, Sluyter R Pharmaceutics. 2023; 15(9).

PMID: 37765233 PMC: 10536354. DOI: 10.3390/pharmaceutics15092263.

References

Yi T, Zhao D, Lin C, Zhang C, Chen Y, Todorov I . Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease. Blood. 2008; 112(5):2101-10. PMC: 2518909. DOI: 10.1182/blood-2007-12-126987. View

Litjens N, van de Wetering J, van Besouw N, Betjes M . The human alloreactive CD4+ T-cell repertoire is biased to a Th17 response and the frequency is inversely related to the number of HLA class II mismatches. Blood. 2009; 114(18):3947-55. DOI: 10.1182/blood-2009-03-211896. View

Pene J, Chevalier S, Preisser L, Venereau E, Guilleux M, Ghannam S . Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol. 2008; 180(11):7423-30. DOI: 10.4049/jimmunol.180.11.7423. View

Socie G, Blazar B . Acute graft-versus-host disease: from the bench to the bedside. Blood. 2009; 114(20):4327-36. PMC: 2777122. DOI: 10.1182/blood-2009-06-204669. View

Lochner M, Peduto L, Cherrier M, Sawa S, Langa F, Varona R . In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells. J Exp Med. 2008; 205(6):1381-93. PMC: 2413035. DOI: 10.1084/jem.20080034. View

Murata H, Janin A, Leboeuf C, Soulier J, Gluckman E, Meignin V . Donor-derived cells and human graft-versus-host disease of the skin. Blood. 2006; 109(6):2663-5. DOI: 10.1182/blood-2006-07-033902. View

McGeachy M, Cua D . Th17 cell differentiation: the long and winding road. Immunity. 2008; 28(4):445-53. DOI: 10.1016/j.immuni.2008.03.001. View

Rieger K, Loddenkemper C, Maul J, Fietz T, Wolff D, Terpe H . Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood. 2005; 107(4):1717-23. DOI: 10.1182/blood-2005-06-2529. View

Chen X, Vodanovic-Jankovic S, Johnson B, Keller M, Komorowski R, Drobyski W . Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease. Blood. 2007; 110(10):3804-13. PMC: 2077325. DOI: 10.1182/blood-2007-05-091074. View

10.

Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y . Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2002; 52(1):65-70. PMC: 1773503. DOI: 10.1136/gut.52.1.65. View

11.

Laurence A, OShea J . T(H)-17 differentiation: of mice and men. Nat Immunol. 2007; 8(9):903-5. DOI: 10.1038/ni0907-903. View

12.

Koenen H, Smeets R, Vink P, van Rijssen E, Boots A, Joosten I . Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood. 2008; 112(6):2340-52. DOI: 10.1182/blood-2008-01-133967. View

13.

Zhang C, Zhang J, Yang B, Wu C . Cyclosporin A inhibits the production of IL-17 by memory Th17 cells from healthy individuals and patients with rheumatoid arthritis. Cytokine. 2008; 42(3):345-52. DOI: 10.1016/j.cyto.2008.03.006. View

14.

Yi T, Chen Y, Wang L, Du G, Huang D, Zhao D . Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease. Blood. 2009; 114(14):3101-12. PMC: 2756212. DOI: 10.1182/blood-2009-05-219402. View

15.

Bettelli E, Korn T, Oukka M, Kuchroo V . Induction and effector functions of T(H)17 cells. Nature. 2008; 453(7198):1051-7. PMC: 6280661. DOI: 10.1038/nature07036. View

16.

Sakai A, Sugawara Y, Kuroishi T, Sasano T, Sugawara S . Identification of IL-18 and Th17 cells in salivary glands of patients with Sjögren's syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol. 2008; 181(4):2898-906. DOI: 10.4049/jimmunol.181.4.2898. View

17.

Brand S . Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease. Gut. 2009; 58(8):1152-67. DOI: 10.1136/gut.2008.163667. View

18.

Kappel L, Goldberg G, King C, Suh D, Smith O, Ligh C . IL-17 contributes to CD4-mediated graft-versus-host disease. Blood. 2008; 113(4):945-52. PMC: 2630280. DOI: 10.1182/blood-2008-08-172155. View

19.

Christodoulou M, Kapsogeorgou E, Moutsopoulos N, Moutsopoulos H . Foxp3+ T-regulatory cells in Sjogren's syndrome: correlation with the grade of the autoimmune lesion and certain adverse prognostic factors. Am J Pathol. 2008; 173(5):1389-96. PMC: 2570129. DOI: 10.2353/ajpath.2008.080246. View

20.

Carlson M, West M, Coghill J, Panoskaltsis-Mortari A, Blazar B, Serody J . In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations. Blood. 2008; 113(6):1365-74. PMC: 2637199. DOI: 10.1182/blood-2008-06-162420. View