Noelle RJ, Nowak ECCellular sources and immune functions of interleukin-9. Nat Rev Immunol 10:683-687

Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Nature Reviews Immunology (Impact Factor: 34.99). 10/2010; 10(10):683-7. DOI: 10.1038/nri2848
Source: PubMed


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, Fallon et al. [64] have shown that despite a lack of IL-4, IL-5, IL-9 and IL-13 gene activity and compromised Th2 responses, female mice reproduce successfully even during an allogeneic pregnancy [65]. IL-9 is a pleiotropic cytokine with direct and indirect effects on many cell types involved in immunity and inflammation [62], [66], [67]. IL-9 seems to be required for allergic inflammation in the lung as well as other tissues, but it also provides protective immunity to intestinal parasites [63]. "
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    ABSTRACT: Despite much interest in the mechanisms regulating fetal-maternal interactions, information on leukocyte populations and major cytokines present in uterus and placenta remains fragmentary. This report presents a detailed and quantitative study of leukocyte populations at the mouse fetal-maternal interface, including a comparison between pregnancies from syngeneic and allogeneic crosses. Our results provide evidence for drastic differences not only in the composition of leukocyte populations in the uterus during pregnancy, but also between uterine and placental tissues. Interestingly, we have observed a significant decrease in the number of myeloid Gr1+ cells including monocytes, and myeloid CD11c+ cells including DCs in placenta from an allogeneic pregnancy. In addition, we have compared the expression levels of a panel of cytokines in non-pregnant (NP) or pregnant mouse uterus, in placenta, or in their isolated resident leukocytes. Qualitative and quantitative differences have emerged between NP, pregnant uterus and placenta. Unexpectedly, IL-9 was the major cytokine in NP uterus, and was maintained at high levels during pregnancy both in uterus and placenta. Moreover, we have found that pregnancy is associated with an increase in uterine IL-1a and a significant decrease in uterine G-CSF and GM-CSF. Comparing allogeneic versus syngeneic pregnancy, less allogeneic placental pro-inflammatory cytokines CCL2 (MCP-1), CXCL10 (IP-10) and more IL1-α in whole uterus was reproducibly observed. To our knowledge, this is the first report showing a detailed overview of the leukocyte and cytokine repertoire in the uterus of virgin females and at the fetal-maternal interface, including a comparison between syngeneic and allogeneic pregnancy. This is also the first evidence for the presence of IL-9 in NP uterus and at the maternal-fetal interface, suggesting a major role in the regulation of local inflammatory or immune responses potentially detrimental to the conceptus.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "IL-9 was originally identified as a T cell growth factor and it is a member of the common-γ-chain-receptor cytokine family including IL-2, IL-4, IL-7, IL-15 and IL-21. The activation of IL-9 receptor α-γ-chain induces activation of JAK/1–3 and downstream STAT1/3 and STAT528. It has been demonstrated that IL-9 induces SOCS3 which then limits IL-9 signaling29. "
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    ABSTRACT: In a murine model of allergic asthma, we found that Tyk-2((-/-)) asthmatic mice have induced peribronchial collagen deposition, mucosal type mast cells in the lung, IRF4 and hyperproliferative lung Th2 CD4(+) effector T cells over-expressing IL-3, IL-4, IL-5, IL-10 and IL-13. We also observed increased Th9 cells expressing IL-9 and IL-10 as well as T helper cells expressing IL-6, IL-10 and IL-21 with a defect in IL-17A and IL-17F production. This T helper phenotype was accompanied by increased SOCS3 in the lung of Tyk-2 deficient asthmatic mice. Finally, in vivo treatment with rIL-17A inhibited local CD4(+)CD25(+)Foxp3(+) T regulatory cells as well as Th2 cytokines without affecting IL-9 in the lung. These results suggest a role of Tyk-2 in different subsets of T helper cells mediated by SOCS3 regulation that is relevant for the treatment of asthma, cancer and autoimmune diseases.
    Full-text · Article · Aug 2014 · Scientific Reports
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    • "IL-9 has attracted renewed interest since its expression was identified in multiple T helper (Th) cell subsets (including Th2, Th9, Th17), regulatory T cells (Treg) and natural killer (NK)/T cells [7]. Several studies have indicated that IL-9 may promote oncogenesis during Hodgkin's Lymphoma (HL) and large cell anaplastic lymphoma [8]–[10] in addition to its significant regulatory role in allergy and autoimmunity [11]–[13]. "
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    ABSTRACT: Interleukin-9 (IL-9) is more functionally diverse than previously expected, especially with regards to lymphomagenesis. However, the relationship between IL-9 and the clinicopathological features of extranodal NK/T-cell lymphoma is less well established. Patients with this lymphoma in Sun Yat-Sen University Cancer Center between January 2003 and March 2013 were systematically reviewed in an intention-to-treat analysis. Baseline serum IL-9 levels were determined using sandwich enzyme-linked immunosorbent assays. A total of seventy-four patients were enrolled in this study. The mean concentration of serum IL-9 for all patients was 6.48 pg/mL (range: 1.38-51.87 pg/mL). Age, B symptoms and local lymph node involvement were found to be related to high serum IL-9 levels. Patients with low IL-9 levels tended to have higher rates of complete remission. Notably, the median progression-free survival (PFS) and overall survival (OS) were longer in the low IL-9 level group than in the high IL-9 level group (PFS: 68.7 months vs. 28.3 months, P<0.001; OS: 86 months vs. 42.8 months, P = 0.001). Multivariate analysis revealed independent prognostic factors for PFS. Similarly, high IL-9 levels (P = 0.003) and old age (P = 0.007) were independently predictive of shorter OS. Serum IL-9 is closely related to several clinical features, such as age, B symptoms and local lymph node involvement. It can also be a significant independent prognostic factor for extranodal NK/T-cell lymphoma, which suggests a role for IL-9 in the pathogenesis of this disease and offers new insight into potential therapeutic strategies.
    Full-text · Article · Apr 2014 · PLoS ONE
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