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      The Alteration and Clinical Significance of Th22/Th17/Th1 Cells in Patients with Chronic Myeloid Leukemia

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          Abstract

          T helper- (Th-) cell immunodeficiency plays important roles in tumor development and their effects in chronic myeloid leukemia (CML) remain unclear. In the present study, we mainly investigated the role of Th22, Th17, and Th1 cell and their related cytokines (IL-22, IL-17, and IFN-r) in the pathophysiology of CML. Bone marrow (BM) and peripheral blood (PB) were extracted from newly diagnosed (ND), chronic phase- (CP-) CML patients, and controls. Th subsets were examined by flow cytometry. Plasma IL-22, IL-17, and IFN-r concentrations were measured by ELISA. AHR and RORC mRNA expressions were examined by RT-PCR. The frequencies of Th22, Th17, and Th1 cells, along with the expression of specific transcription factors RORC and AHR, were significantly decreased in ND patients compared with healthy controls, while all these abnormality recovered in CP patients. In addition, there existed a significantly positive relationship between Th22 and Th17 cells in PB or BM. A significantly negative relationship was found between Th cells (Th22, Th17, or Th1) and BCR-ABL (%) IS or the number of PB white blood cells. All these results demonstrated that Th22, Th17, and Th1 cells might be important therapeutic targets in CML and could facilitate a better outcome for tumor immunotherapy.

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          Most cited references24

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          A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.

          Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-gamma negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.
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            Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells.

            Interleukin 22 (IL-22) is a cytokine produced by the T(H)-17 lineage of helper T cells and NK-22 subset of natural killer cells that acts on epithelial cells and keratinocytes and has been linked to skin homeostasis and inflammation. Here we characterize a population of human skin-homing memory CD4(+) T cells that expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but neither IL-17 nor interferon-gamma (IFN-gamma). Clones isolated from this population produced IL-22 only and had low or undetectable expression of the T(H)-17 and T helper type 1 (T(H)1) transcription factors RORgammat and T-bet. The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor-dependent way. Our findings delineate a previously unknown subset of human CD4(+) effector T cells dedicated to skin pathophysiology.
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              The biology of chronic myeloid leukemia.

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                Author and article information

                Journal
                J Immunol Res
                J Immunol Res
                JIR
                Journal of Immunology Research
                Hindawi Publishing Corporation
                2314-8861
                2314-7156
                2015
                27 April 2015
                : 2015
                : 416123
                Affiliations
                1Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China
                2Department of Hematology, Jinan Central Hospital, Shandong University, Jinan 250013, China
                Author notes

                Academic Editor: Patrizia D'Amelio

                Article
                10.1155/2015/416123
                4427092
                26000313
                3152ee9e-c6ba-4d7f-9a75-bd52865f1b97
                Copyright © 2015 Ping Chen et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 October 2014
                : 29 January 2015
                Categories
                Research Article

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