Cellular Mediators of Inflammation: Tregs and TH17 Cells in Gastrointestinal Diseases

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2010 Feb 20

PMID 20169125

Citations 17

Authors

Franco Pandolfi

Rossella Cianci

Danilo Pagliari

Raffaele Landolfi

Giovanni Cammarota

Affiliations

Soon will be listed here.

Abstract

Human lymphocyte subpopulations were originally classified as T- and B-cells in the 70s. Later, with the development of monoclonal antibodies, it became possible to recognize, within the T-cells, functional populations: CD4(+) and CD8(+). These populations were usually referred to as "helper" and "suppressor" cells, respectively. However several investigations within the CD8 cells failed to detect a true suppressor activity. Therefore the term suppressor was neglected because it generated confusion. Much later, true suppressor activity was recognized in a subpopulation of CD4 cells characterized by high levels of CD25. The novel population is usually referred to as T regulatory cells (Tregs) and it is characterized by the expression of FoxP3. The heterogeneity of CD4 cells was further expanded by the recent description of a novel subpopulation characterized by production of IL-17. These cells are generally referred to as T(H)17. They contribute to regulate the overall immune response together with other cytokine-producing populations. Treg and T(H)17 cells are related because they could derive from a common progenitor, depending on the presence of certain cytokines. The purpose of this review is to summarize recent findings of the role of these novel populations in the field of human gastroenterological disease.

Citing Articles

Gut Microbiota, Inflammatory Bowel Disease, and Cancer: The Role of Guardians of Innate Immunity.

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The Role of Gut Microbiota in Heart Failure: When Friends Become Enemies.

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Carbamylated erythropoietin regulates immune responses and promotes long-term kidney allograft survival through activation of PI3K/AKT signaling.

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References

Ichihara F, Kono K, Takahashi A, Kawaida H, Sugai H, Fujii H . Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers. Clin Cancer Res. 2003; 9(12):4404-8. View

Chew V, Tow C, Teo M, Wong H, Chan J, Gehring A . Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients. J Hepatol. 2009; 52(3):370-9. DOI: 10.1016/j.jhep.2009.07.013. View

Sakaguchi S, Powrie F . Emerging challenges in regulatory T cell function and biology. Science. 2007; 317(5838):627-9. DOI: 10.1126/science.1142331. View

Komatsu N, Mariotti-Ferrandiz M, Wang Y, Malissen B, Waldmann H, Hori S . Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc Natl Acad Sci U S A. 2009; 106(6):1903-8. PMC: 2644136. DOI: 10.1073/pnas.0811556106. View

Kanai T, Nemoto Y, Kamada N, Totsuka T, Hisamatsu T, Watanabe M . Homeostatic (IL-7) and effector (IL-17) cytokines as distinct but complementary target for an optimal therapeutic strategy in inflammatory bowel disease. Curr Opin Gastroenterol. 2009; 25(4):306-13. DOI: 10.1097/MOG.0b013e32832bc627. View

OConnor Jr W, Kamanaka M, Booth C, Town T, Nakae S, Iwakura Y . A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol. 2009; 10(6):603-9. PMC: 2709990. DOI: 10.1038/ni.1736. View

Workman C, Szymczak-Workman A, Collison L, Pillai M, Vignali D . The development and function of regulatory T cells. Cell Mol Life Sci. 2009; 66(16):2603-22. PMC: 2715449. DOI: 10.1007/s00018-009-0026-2. View

Zenewicz L, Antov A, Flavell R . CD4 T-cell differentiation and inflammatory bowel disease. Trends Mol Med. 2009; 15(5):199-207. DOI: 10.1016/j.molmed.2009.03.002. View

Bennett W, Pandolfi F, Grove B, Hawes G, Boyle L, Kradin R . Dominant rearrangements among human tumor-infiltrating lymphocytes. Analysis of T-cells derived from 32 patients with melanoma, lung, and renal cell carcinoma. Cancer. 1992; 69(9):2379-84. DOI: 10.1002/1097-0142(19920501)69:9<2379::aid-cncr2820690928>3.0.co;2-w. View

10.

Hiraoka N, Onozato K, Kosuge T, Hirohashi S . Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006; 12(18):5423-34. DOI: 10.1158/1078-0432.CCR-06-0369. View

11.

Sojka D, Huang Y, Fowell D . Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. Immunology. 2008; 124(1):13-22. PMC: 2434375. DOI: 10.1111/j.1365-2567.2008.02813.x. View

12.

Strober W, Fuss I, Mannon P . The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007; 117(3):514-21. PMC: 1804356. DOI: 10.1172/JCI30587. View

13.

Kono K, Kawaida H, Takahashi A, Sugai H, Mimura K, Miyagawa N . CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother. 2005; 55(9):1064-71. PMC: 11030626. DOI: 10.1007/s00262-005-0092-8. View

14.

Abbas A, Lohr J, Knoechel B, Nagabhushanam V . T cell tolerance and autoimmunity. Autoimmun Rev. 2004; 3(7-8):471-5. DOI: 10.1016/j.autrev.2004.07.004. View

15.

Stephens L, Mottet C, Mason D, Powrie F . Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro. Eur J Immunol. 2001; 31(4):1247-54. DOI: 10.1002/1521-4141(200104)31:4<1247::aid-immu1247>3.0.co;2-m. View

16.

Langowski J, Zhang X, Wu L, Mattson J, Chen T, Smith K . IL-23 promotes tumour incidence and growth. Nature. 2006; 442(7101):461-5. DOI: 10.1038/nature04808. View

17.

Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A, Giometto R . Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007; 110(4):1225-32. DOI: 10.1182/blood-2006-12-064527. View

18.

Zhou X, Bailey-Bucktrout S, Jeker L, Penaranda C, Martinez-Llordella M, Ashby M . Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol. 2009; 10(9):1000-7. PMC: 2729804. DOI: 10.1038/ni.1774. View

19.

Deaglio S, Dwyer K, Gao W, Friedman D, Usheva A, Erat A . Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007; 204(6):1257-65. PMC: 2118603. DOI: 10.1084/jem.20062512. View

20.

Dong C . Differentiation and function of pro-inflammatory Th17 cells. Microbes Infect. 2009; 11(5):584-8. PMC: 2698049. DOI: 10.1016/j.micinf.2009.04.001. View