Cellular sources and immune functions of interleukin-9.
ABSTRACT Interleukin-9 (IL-9) has attracted renewed interest owing to the identification of its expression by multiple T helper (T(H)) cell subsets, including T(H)2 cells, T(H)9 cells, T(H)17 cells and regulatory T (T(Reg)) cells. Here, we provide a broad overview of the conditions that are required for cells to produce IL-9 and describe the cellular targets and nature of the immune responses that are induced by IL-9.
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- "Interestingly, polarized Th2 cells can be deviated into Th9 cells by exposure to TGF-β, which results in down-regulation of GATA-3 and loss of IL-4 and IL-5 production . Using various gene knockout and transgenic mouse systems, Th9 cells have been shown to contribute to autoimmune and allergic inflammation processes (Noelle and Nowak, 2009). However, one recent study identified Th9 cells in healthy human blood and skin and also in metastatic lesions of patients with stage IV melanoma (Purwar et al., 2012). "
ABSTRACT: The importance of CD4 T cells in orchestrating the immune system and their role in inducing effective T cell-mediated therapies for the treatment of patients with select established malignancies are undisputable. Through a complex and balanced array of direct and indirect mechanisms of cellular activation and regulation, this functionally diverse family of lymphocytes can potentially promote tumor eradication, long-term tumor immunity, and aid in establishing and/or rebalancing immune cell homeostasis through interaction with other immune cell populations within the highly dynamic tumor environment. However, recent studies have uncovered additional functions and roles for CD4 T cells, some of which are independent of other lymphocytes, that can not only influence and contribute to tumor immunity but paradoxically promote tumor growth and progression. Here, we review the recent advances in our understanding of the various CD4 T cell lineages and their signature cytokines in disease progression and/or regression. We discuss their direct and indirect mechanistic interplay among themselves and with other responding cells of the antitumor response, their potential roles and abilities for "plasticity" and memory cell generation within the hostile tumor environment, and their potentials in cancer treatment and immunotherapy.Frontiers in Oncology 03/2013; 3:63. DOI:10.3389/fonc.2013.00063
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- "However, TAMs seem to play a decisive role in the induction of Treg response as TAMs induced the production of TGF-␤ (the marker cytokine for Treg) by naïve CD4 + T cells (Fig. 2b). Evidences suggest that a unique cytokine pattern is associated with the induction of a specific T cell response (Noelle and Nowak 2010). Herein, we disclose that MDSCs mediated induction of IL-17 + T cell is independent of MDSC-T cell contact but crucially depends on the cytokines secreted by MDSCs as substantiated by the fact that addition of cell free supernatant of MDSCs or transwell culture of MDSCs with T cells were highly efficient of polarizing naïve T cells toward IL-17 producing type (Fig. 4a). "
ABSTRACT: IL-17 producing CD4(+) T cells (Th17) are identified as a subset of proinflammatory T cells present at the tumor site of various murine and human cancer cases and plays a crucial role in shaping the neoplastic process through fostering tumor angiogenesis and metastasis. However, the development of Th17 response in the tumor microenvironment has not yet been fully elucidated. Herein, we make an attempt to disclose the involvement of tumor infiltrating antigen presenting cells (APCs), especially tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs) to polarize naïve CD4(+) T cells toward IL-17(+) T cells. We have found that MDSCs either isolated from the tumor site or generated in vitro are superior over TAMs to induce IL-17 production by naïve CD4(+) T cells. Furthermore, we have shown that MDSCs mediated induction of IL-17(+) T cell response is independent of MDSCs-T cell contact but crucially depends on the cytokines secreted by MDSCs. Our study will help to develop potential therapeutic strategies by harnessing the ability of MDSCs to induce IL-17 production by CD4(+) T cells and thus restrict the generation of inflammatory Th17 population at the disease site.Immunobiology 08/2012; DOI:10.1016/j.imbio.2012.08.271 · 3.18 Impact Factor
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- "The scenario becomes more complex when other functional subsets are being proposed according to the cytokine they produced and their functional effects. Thus, additional regulatory T cells, such as Tr1 (TGFb) or Tr3 (IL-10), as well as other Th cells, such as Th9 (IL-9) or Th22 (IL-22) have recently been described  . "
ABSTRACT: Aging is accompanied by a progressive increase in pro-inflammatory cytokine status. However, little is known about the development of age-dependent modifications in other circulating cytokines. The aim of this study was to investigate in vivo the influence of age on circulating cytokine production in healthy subjects (HC). Circulating cytokines were measured by CBA and ELISA in 73 HC. Intracellular cytokine production was assessed in CD3+ and CD14+ cells by flow cytometry. Production of cytokines in cell culture supernatants was also studied after polyclonal stimulation. Subjects were divided into three different groups according to age: 28 young HC (<30 years, 26.2 ± 2.4), 24 middle age HC (30-60 years, 44.7 ± 8.4) and 21 elderly HC (>60 years, 70.6 ± 7.9). Age was positively correlated with the circulating levels of IL-12p70, IL-1β, TNFα, IL-6, and IL-10. Age had a negative correlation with circulating levels of IL-17. Besides, age was positively correlated with spontaneous intracellular expression of proinflammatory cytokines in circulating monocytes. No correlation was found with other intracellular cytokine expression or with the production of cytokines in cell culture supernatants after in vitro stimulation. Gender had a marginal effect on the circulating cytokine profile. Aging has a significant impact on the production of circulating cytokines in healthy individuals. The circulating cytokine milieu may contribute to the development of age-restricted conditions.Cellular Immunology 01/2012; 273(2):124-32. DOI:10.1016/j.cellimm.2012.01.001 · 1.87 Impact Factor