Disease relevance of Il9

• We have used mice genetically deficient in IL-9 to determine the role of this cytokine in the pathophysiologic features of the allergic pulmonary response-airway hyperreactivity (AHR) and eosinophilia [1].
• Goblet cell hyperplasia and immunoglobulin (Ig) E production were also unaffected by the lack of IL-9 [1].
• The absence of interleukin 9 does not affect the development of allergen-induced pulmonary inflammation nor airway hyperreactivity [1].
• Interleukin-9 is a major anti-apoptotic factor for thymic lymphomas [2].
• In this study we demonstrate that IL-9 is expressed early during the Th2-type response and that its elevation in vivo results in the enhancement of intestinal mastocytosis and the production of both the immunoglobulin E (IgE) and IgG1 isotypes [3].

High impact information on Il9

• The gamma-chain is also a critical signaling component of IL-4, IL-7 and IL-9 receptors [4].
• By contrast, for expression of more mature action potentials (tetrodotoxin-sensitive) one of the interleukins IL-5, IL-7 or IL-9 must be applied in association with transforming growth factor-alpha after pretreatment with basic fibroblast growth factor [5].
• Functional redundancy is highly prevalent among the Th2 interleukins (IL)-4, IL-5, IL-9, and IL-13 [6].
• IL-9 was not required for T cell development or differentiation, the generation of naive or antigen-driven antibody responses, or the expulsion of the intestinal parasitic nematode Nippostrongylus brasiliensis [7].
• Thus, deletion of IL-9 manifests as a highly defined phenotype in Th2 responses modulating mucus production and mast cell proliferation [7].

Chemical compound and disease context of Il9

• In this study, an antimouse IL-9 (anti-mIL-9) antibody (Ab) was evaluated against pulmonary eosinophilia, histopathologic changes in lung tissues, serum immunoglobulin (Ig) E levels, and airway hyperresponsiveness (AHR) to methacholine in mice sensitized and challenged with ovalbumin (OVA) [8].
• Intracerebral injection of the glutamatergic analogue ibotenate to newborn mice induces cortical plate and white matter lesions mimicking the brain damage associated with cerebral palsy, and pretreatment with proinflammatory cytokines such as interleukin-1-beta or with interleukin-9 significantly exacerbates these lesions [9].
• Histamine and IL-9 are suspected to play an important role in the pathogenesis of asthmatic and allergic reactions [10].

Biological context of Il9

• Taken together, these results show that cytokines such as IL-9 can regulate the expression of a member of the RAS family possibly involved in growth-factor signal transduction [11].
• Moreover, IL-9 stimulation or BCL3 transient transfection similarly inhibited NF-kappaB-mediated transcription in response to TNF [12].
• Contrasting with the potent upregulation of M-Ras expression, M-Ras was not activated by IL-9 at the level of guanosine triphosphate/guanosine diphosphate (GTP/GDP) binding [11].
• Taken together, our results indicate that IL-9 induces a mast cell-like phenotype in T cell clones [13].
• Here we show that IL-4 and IL-9 induce overlapping (170, 130, and 125 kilodalton (kDa)) and distinct (45 and 88/90 kDa, respectively) protein tyrosine phosphorylation in T lymphocytes [14].

Anatomical context of Il9

• Interleukin (IL)-4 and IL-9 regulate the proliferation of T lymphocytes through interactions with their receptors [14].
• In addition, other proteases such as the mouse mast cell proteases were also found to be expressed by IL-9-activated T cell clones [13].
• We used 15 IL-9 transgenic mice and eight corresponding wild-type mice (FVB/N) and transplanted them with NPM/ALK infected bone marrow cells [15].
• Interleukin 9-induced in vivo expansion of the B-1 lymphocyte population [16].
• Analysis of B cell populations showed a specific expansion of Mac-1(+) B-1 cells in the peritoneal and pleuropericardial cavities, and in the blood of IL-9 transgenic mice [16].

Associations of Il9 with chemical compounds

• We have demonstrated that IL-9 is not required for the development of a robust Th2 response to allergen in sensitized mice [1].
• Moreover, IL-4 and IL-9 maintained proliferation of these cells in the presence of DEX [2].
• Previous studies have shown that unknown tyrosine kinases are involved in the proliferative signaling triggered by IL-4 and IL-9 [14].
• However, IL-9 acted synergistically with IL-7 and PHA to stimulate the proliferation of irradiated cells during the second post-irradiation phase [17].
• In addition, IL-9, -13, and -15 were significantly elevated only following toluene diisocyanate exposure [18].

Physical interactions of Il9

• Finally, we compared the fate of major histocompatibility complex class II-mismatched cardiac transplants from wild-type versus IL-9 transgenic donors to determine the influence of IL-9 overexpression within the graft [19].

Regulatory relationships of Il9

• By Northern blot hybridization and functional assays, we found that IL-9 induced the expression of granzyme B in several T cell clones as well as in mast cell lines [13].
• Interleukin-9 stimulates the production of interleukin-5 in CD4+ T cells [20].
• Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction [12].
• Taken together, these results indicate that IL-4 may serve as a growth-promoting factor for hematopoietic stem cells, and IL-9 enhances both growth and erythroid differentiation of primitive hematopoietic progenitors [21].
• Both KL and IL-10 considerably enhance the production of IL-9 mRNA and protein [22].
• Although IL-9-induced eosinophilia in the peritoneal cavity was not diminished in the absence of IL-13, IL-13 was required for IL-9 to increase eotaxin expression and lung eosinophilia [23].

Other interactions of Il9

• A significant inverse correlation between lung Ugrp1 mRNA levels and IL-9 levels in BAL fluid was demonstrated by regression analysis (r = 0.616, P = 0.023) [24].
• However, IL-3 increased GTP binding to M-Ras, suggesting that M-Ras induction might represent a new mechanism of cooperativity between cytokines such as IL-3 and IL-9 [11].
• In addition, we demonstrate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor [14].
• This observation led us to investigate the functional link between IL-9 and IL-5 production during alloreactive T cell responses in vitro and in vivo [20].
• To characterize the specificity of IL-9-mediated T cell activation, we used a murine T cell clone that could grow with either IL-9 or IL-2 [13].

Analytical, diagnostic and therapeutic context of Il9

• Eight IL-9 transgenic mice, serving as a control group, received pLXSN (vector only)-infected marrow [15].
• IL-9 transgenic mice were chosen as the animal model system, because dysregulated expression of the IL-9 gene in transgenic mice results in the sporadic development of spontaneous thymic lymphomas [15].
• A severe airway inflammation accompanied by airway eosinophilia and elevation of IL-9 in bronchoalveolar lavage (BAL) fluids was observed after ovalbumin (OVA) challenge to OVA-sensitized mice [24].
• Intranasal administration of IL-9 to naive mice decreased the level of Ugrp1 expression in lungs [24].
• Overall, this paper demonstrates that dendritic cell vaccination can be used to successfully protect the host against intestinal nematode infection and suggests that IL-9 can act as a potent type 2 adjuvant during Ag presentation and the early stages of Th2 activation [25].

References