Biomedical subjects

J C Renauld

Publications and source records attributed to J C Renauld.

At least 37 records · Page 2Linked to original sources

PubMed2000

Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice.

Production of neutralizing anti-IL-9 antibodies was induced in mice by immunization with mouse IL-9 coupled to ovalbumin. In the six mouse strains tested, a strong and long-lasting anti-IL-9 response developed with seric inhibitory titers of 10(-3) to 10(-5), as measured in an in vitro IL-9-dependent cell proliferation assay. In vivo, this immunization completely abrogated the increase in mast-cell protease-1 levels as well as the eosinophilia observed in mice after implantation of an IL-9-secreting tumor. We took advantage of this method to assess the role of IL-9 in infections with nematode Trichuris muris, where IL-9 production correlates with the resistant phenotype. C57BL/6 mice, which normally expel the parasite, became susceptible after anti-IL-9 immunization, demonstrating that IL-9 plays a critical role in this model. In addition, neutralization of IL-9 also inhibited parasite-induced blood eosinophilia. Taken together, the present data demonstrate the potency of our strategy to antagonize IL-9 in vivo and shows that this cytokine plays a major role in resistance against T. muris infection.

Animals↗

PubMed2000

Interleukin-10 blockade corrects impaired in vitro cellular immune responses of systemic lupus erythematosus patients.

OBJECTIVE: Many systemic lupus erythematosus (SLE) patients display impaired cellular immune responses against allo- or recall antigens. Given the down-regulating properties of interleukin-10 (IL-10) on antigen-presenting cell functions, this study was undertaken to investigate whether the well-known overproduction of IL-10 by SLE peripheral blood mononuclear cells (PBMC) was involved in this process. METHODS: We measured the proliferation of SLE or control PBMC against irradiated allogeneic dendritic cells in the absence or presence of antibodies blocking IL-10 activity, or in the absence or presence of IL-12. RESULTS: As a group, SLE PBMC proliferated against allogeneic targets less than control PBMC. However, SLE patients could be categorized as good responders or poor responders according to the amplitude of their allogeneic response. Interestingly, serum IL-10 concentrations were significantly higher in the poor responders than in the good responders or in the controls, and addition of antibodies blocking IL-10 activity significantly increased the proliferative responses of the group. We confirmed the role of IL-10 in the impaired allogeneic responses displayed by SLE PBMC by demonstrating that addition of IL-10-containing SLE PBMC supernatants inhibited a normal allogeneic response between unrelated healthy controls, and by showing that this inhibitory effect was commensurate with the concentrations of IL-10 measured in the supernatants. In this experimental setting, we also demonstrated that IL-10-containing SLE PBMC supernatants inhibited IL-12 p35 and IL-12 p40 gene expression. Consistent with the last observation, we found that addition of exogenous IL-12 restored the proliferation of poor-responder SLE patients' PBMC. CONCLUSION: Taken together, these results indicate that dysregulation of the IL-10/IL-12 balance plays a critical role in the impaired cellular immune responses observed in SLE patients.

Adolescent↗

PubMed2000

An animal model for anaplastic large cell lymphoma in the immunocompetent syngeneic C57Bl/6 mouse.

We report on the analysis of a murine anaplastic lymphoid cell line TS1G6, established recently by interleukin (IL)-9 transfection. TS1G6 revealed a highly characteristic pattern of large anaplastic cells with mononuclear, binuclear, or multinuclear cells resembling Hodgkin (H) or Sternberg-Reed (SR) cells. This cell line is tumorigenous after injection of as few as 10(4) lymphoma cells into nude or immunocompetent C57Bl/6 mice and leads to death from progressive disease of all treated animals within a few weeks. The histological analysis of these tumors revealed a diffuse large cell malignant lymphoma that is morphologically almost identical to human anaplastic large cell lymphoma (ALCL). The lymphoma cells did not show overexpression of the anaplastic lymphoma kinase (ALK) gene, which is found in about 50% of the cases of human ALCL. Thus, this model may be an animal model for an important subset of human ALCL. The cytokine profile, which is of the T helper 2 type, showed strong parallels to the human lymphoma counterpart. Mice suffering from such lymphomas could not be cured with a regimen using high dose cyclophosphamide similar to many ALCL patients. Such an animal model for ALCL has not yet been recognized, but may provide the basis for investigating new antitumor immunotherapies in a fully immunocompetent host.

Anaplastic Lymphoma Kinase↗

PubMed2000

IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes.

IL-TIF is a new cytokine originally identified as a gene induced by IL-9 in murine T lymphocytes, and showing 22% amino acid identity with IL-10. Here, we report the sequence and organization of the mouse and human IL-TIF genes, which both consist of 6 exons spreading over approximately 6 Kb. The IL-TIF gene is a single copy gene in humans, and is located on chromosome 12q15, at 90 Kb from the IFN gamma gene, and at 27 Kb from the AK155 gene, which codes for another IL-10-related cytokine. In the mouse, the IL-TIF gene is located on chromosome 10, also in the same region as the IFN gamma gene. Although it is a single copy gene in BALB/c and DBA/2 mice, the IL-TIF gene is duplicated in other strains such as C57Bl/6, FVB and 129. The two copies, which show 98% nucleotide identity in the coding region, were named IL-TIF alpha and IL-TIF beta. Beside single nucleotide variations, they differ by a 658 nucleotide deletion in IL-TIF beta, including the first non-coding exon and 603 nucleotides from the promoter. A DNA fragment corresponding to this deletion was sufficient to confer IL-9-regulated expression of a luciferase reporter plasmid, suggesting that the IL-TIF beta gene is either differentially regulated, or not expressed at all.

Animals↗

PubMed2000

Expression of interleukin-9 leads to Th2 cytokine-dominated responses and fatal enteropathy in mice with chronic Schistosoma mansoni infections.

Mice infected with Schistosoma mansoni develop Th2 cytokine-mediated granulomatous pathology that is focused on the liver and intestines. In this study, transgenic mice constitutively expressing IL-9 were infected with S. mansoni and the outcome of infection was determined. Eight weeks after infection, transgenic mice with acute infections had a moderate increase in Th2 cytokine production but were overtly normal with respect to parasite infection and pathological responses. Transgenic mice with chronic infections died 10 weeks after infection, with 86% of transgenic mice dead by week 12 of infection, compared to 7% mortality in infected wild-type mice. Stimulation of mesenteric lymph node cells from infected transgenic mice with parasite antigen elicited elevated interleukin-4 (IL-4) and IL-5 production and reduced gamma interferon and tumor necrosis factor alpha production compared to the responses in wild-type mice. Morbid transgenic mice had substantial enlargement of the ileum, which was associated with muscular hypertrophy, mastocytosis, eosinophilia, goblet cell hyperplasia, and increased mucin expression. We also observed that uninfected transgenic mice exhibited alterations in their intestines. Although there was hepatic mastocytosis and eosinophilia in infected transgenic mice, there was no hepatocyte damage. Death of transgenic mice expressing IL-9 during schistosome infection was primarily associated with enteropathy. This study highlights the pleiotropic in vivo activity of IL-9 and demonstrates that an elevated Th2 cytokine phenotype leads to death during murine schistosome infection.

Animals↗

PubMed2000

Bcl-3 expression promotes cell survival following interleukin-4 deprivation and is controlled by AP1 and AP1-like transcription factors.

We have analyzed the interleukin-4 (IL-4)-triggered mechanisms implicated in cell survival and show here that IL-4 deprivation induces apoptotic cell death but does not modulate Bcl-2 or Bcl-x expression. Since Bcl-x expression is insufficient to ensure cell survival in the absence of IL-4, we speculate that additional molecules replace the antiapoptotic role of Bcl-2 and Bcl-x in an alternative IL-4-triggered pathway. Cell death is associated with Bcl-3 downregulation and Bcl-3 expression blocks IL-4 deprivation-induced apoptosis, suggesting that Bcl-3 acts as a survival factor in the absence of growth factor. To characterize the IL-4-induced regulation of murine Bcl-3 expression, we cloned the promoter of this gene. Sequencing of the promoter showed no TATA box element but did reveal binding sites for AP1, AP1-like, and SP1 transcription factors. Retardation gels showed that IL-4 specifically induces AP1 and AP1-like binding activity and that mutation of these binding sites abolishes the IL-4-induced Bcl-3 promoter activity, suggesting that these transcription factors are important in Bcl-3 promoter transactivation. IL-4 deprivation induces downregulation of Jun expression and upregulation of Fos expression, both of which are proteins involved in the formation of AP1 and AP1-like transcription factors. Overexpression of Jun family proteins transactivates the promoter and restores Bcl-3 expression in the absence of IL-4 stimulation. Taken together, these data describe a new biological role for Bcl-3 and define the regulatory pathway implicated in Bcl-3 expression.

Animals↗

PubMed2000

Interleukin-9 upregulates mucus expression in the airways.

Interleukin (IL)-9 has recently been shown to play an important role in allergic disease because its expression is strongly associated with the degree of airway responsiveness and the asthmatic-like phenotype. IL-9 is a pleiotropic cytokine that is active on many cell types involved in the allergic immune response. Mucus hypersecretion is a clinical feature of chronic airway diseases; however, the mechanisms underlying the induction of mucin are poorly understood. In this report, we show that IL-9 regulates the expression of a subset of mucin genes in lung cells both in vivo and in vitro. In vivo, the constitutive expression of IL-9 in transgenic mice results in elevated MUC2 and MUC5AC gene expression in airway epithelial cells and periodic acid-Schiff-positive staining (reflecting mucous glycogenates). Similar results were observed in C57BL/6J mice after IL-9 intratracheal instillation. In contrast, instillation of the T helper 1-associated cytokine interferon gamma failed to induce mucin production. In vitro, our studies showed that IL-9 also induces expression of MUC2 and MUC5AC in human primary lung cultures and in the human muccoepidermoid NCI-H292 cell line, indicating a direct effect of IL-9 on inducing mucin expression in these cells. Altogether, these results suggest that upregulation of mucin by IL-9 might contribute to the pathogenesis of human inflammatory airway disorders, such as asthma. These data extend the role of the biologic processes that IL-9 has on regulating the many clinical features of asthma and further supports the IL-9 pathway as a key mediator of the asthmatic response.

Animals↗

PubMed2000

Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium.

Many prenatal and perinatal factors are hypothesized to play a role in the cause of cerebral palsy (CP). Epidemiological data implicate maternal-fetal infection and associated increase in circulating cytokines. Murine model data suggest that excitotoxic damage can produce pathological change in brain tissue consistent with lesions observed in CP. Specifically, on day 5 after birth, mouse pups injected with ibotenate, a glutamatergic analogue, develop transcortical necrosis and white matter cysts mimicking some human perinatal lesions associated with CP. The present study builds on this murine model to assess the modulating role of several cytokines on the development of excitotoxic lesions. Pups pretreated with interleukin (IL)-1beta, IL-6, IL-9, or tumor necrosis factor-alpha developed significantly larger ibotenate-induced cortical and white matter damage than controls; IL-4 did not produce such an effect. In a similar manner, IL-9-overexpressing transgenic pups developed ibotenate-induced brain lesions, which were significantly larger than those induced in nontransgenic control pups. Pretreatment with proinflammatory cytokines significantly increased neopallial microglial density without affecting astrocytic density; IL-9 or IL-4 did not produce a similar effect. To our knowledge, this is the first in vivo study to demonstrate that systemically administered proinflammatory cytokines and IL-9 exacerbate brain lesions that are similar to those found in human infants with CP.

Animals↗

PubMed1999

Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9.

Interleukin-9 (IL-9) activates three distinct STAT proteins: STAT1, STAT3, and STAT5. This process depends on one tyrosine of the IL-9 receptor, which is necessary for proliferation, gene induction, and inhibition of apoptosis induced by glucocorticoids. By introduction of point mutations in amino acids surrounding this tyrosine, we obtained receptors that activated either STAT5 alone or both STAT1 and STAT3, thus providing us with the possibility to study the respective roles of these factors in the biological activities of IL-9. Both mutant receptors were able to prevent apoptosis, but only the mutant that activated STAT1 and STAT3 was able to support induction of granzyme A and L-selectin. In line with these results, constitutively activated STAT5 blocked glucocorticoid-induced apoptosis. In Ba/F3 cells, significant proliferation and pim-1 induction were observed with both STAT-restricted mutants, though proliferation was lower than with the wild-type receptor. These results suggest that survival and cell growth are redundantly controlled by multiple STAT factors, whereas differentiation gene induction is more specifically correlated with individual STAT activation by IL-9.

Animals↗

PubMed1999

Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones.

In an attempt to gain insight into the molecular mechanisms involved in interleukin-9 (IL-9) activities, representational difference analysis (RDA) was used to identify messages that are induced by IL-9 in a murine T-helper-cell clone. One of the isolated genes encodes for the newly described M-Ras or R-Ras3, which is part of the Ras gene superfamily. M-Ras expression was found to be induced by IL-9 but not IL-2 or IL-4 in various murine T-helper-cell clones, and this induction seems to be dependent on the JAK/STAT pathway. 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. 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. Constitutively activated M-Ras mutants induced activation of Elk transcription factor by triggering the MAP kinase pathway and allowed for IL-3-independent proliferation of BaF3 cells. 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.

Animals↗

PubMed1999

Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction.

BCL3 encodes a protein with close homology to IkappaB proteins and interacts with p50 NF-kappaB homodimers. However, the regulation and transcriptional activity of BCL3 remain ill-defined. We observed here that interleukin-9 (IL-9) and IL-4, but not IL-2 or IL-3, transcriptionally upregulated BCL3 expression in T cells and mast cells. BCL3 induction by IL-9 was detected as soon as 4 hours after stimulation and appeared to be dependent on the Jak/STAT pathway. IL-9 stimulation was associated with an increase in p50 homodimers DNA binding activity, which was mimicked by stable BCL3 expression. This contrasts with tumor necrosis factor (TNF)-dependent NF-kappaB activation, which occurs earlier, involves p65/p50 dimers, and is dependent on IkappaB degradation. Moreover, IL-9 stimulation or BCL3 transient transfection similarly inhibited NF-kappaB-mediated transcription in response to TNF. Taken together, our observations show a new regulatory pathway for the NF-kappaB transcription factors through STAT-dependent upregulation of BCL3 gene expression.

Animals↗

PubMed1999

Interleukin 9-induced in vivo expansion of the B-1 lymphocyte population.

The activity of interleukin (IL)-9 on B cells was analyzed in vivo using transgenic mice that constitutively express this cytokine. These mice show an increase in both baseline and antigen-specific immunoglobulin concentrations for all isotypes tested. 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. In normal mice, the IL-9 receptor was found to be expressed by CD5(+) as well as CD5(-) B-1 cells, and repeated injections of IL-9 resulted in accumulation of B-1 cells in the peritoneal cavity, as observed in transgenic animals. Unlike other mouse models, such as IL-5 transgenic mice, in which expansion of the B-1 population is associated with high levels of autoantibodies, IL-9 did not stimulate the production of autoantibodies in vivo, and most of the expanded cells were found to belong to the B-1b subset (IgM+Mac-1(+)CD5(-)). In addition, we found that these IL-9-expanded B-1b cells do not share the well-documented antibromelain-treated red blood cell specificity of CD5(+) B-1a cells. The increase of antigen-specific antibody concentration in immunized mice suggests that these B-1 cells are directly or indirectly involved in antibody responses in IL-9 transgenic mice.

Animals↗

PubMed1999

IL-9 induces chemokine expression in lung epithelial cells and baseline airway eosinophilia in transgenic mice.

Recent data have identified IL-9 as a key cytokine in determining susceptibility to asthma. These data are supported by the finding that allergen-exposed IL-9-transgenic mice exhibit many features that are characteristic of human asthma (airway eosinophilia, elevated serum IgE and bronchial hyperresponsiveness) as compared to the background strain. A striking feature of these animals is a robust peribronchial and perivascular eosinophilia after allergen challenge, suggesting that IL-9 is a potent factor in regulating this process. In an attempt to gain insights into the molecular mechanism governing IL-9 modulation of lung eosinophilia, we investigated the ability of this cytokine to induce the expression of CC-type chemokines in the lung because of their effect on stimulating eosinophil chemotaxis. Here we show that IL-9-transgenic mice in contrast to their congenic controls exhibit baseline lung eosinophilia that is associated with the up-regulation of CC-chemokine expression in the airway. This effect appears to be through a direct action of IL-9 because the addition of recombinant IL-9 to primary epithelial cultures and cell lines induced the expression of these chemokines in vitro. These data support a mechanism for IL-9 in regulating the expression of eosinophil chemotactic factors in lung epithelial cells.

Allergens↗

PubMed1999

Synergistic proliferation and activation of natural killer cells by interleukin 12 and interleukin 18.

We investigated the effects of IL-12 and IL-18 on unstimulated murine splenocytes and observed that the two cytokines strongly synergized for their proliferation, whereas IL-12 and IL-18 alone were essentially inactive in this respect. Phenotypical and functional analyses of cells proliferating in response to IL-12 and IL-18 revealed that large granular Ly-49C(+)DX5(+)CD3(-)NK blasts were expanded in these cultures and that they displayed cytotoxic activity against Yac-1 cells, a murine NK cell target. Further analyses indicated three major differences between NK cells appearing in response to IL-12 and IL-18 and those derived in the presence of other NK cell growth factors, such as IL-2 or IL-15. First, a population of T-NK cells, i.e. expressing T cell (TCRalphabeta, CD3) and NK cell (Ly-49) markers, was detected amongst cells growing in IL-2 or IL-15 but not in cultures supplemented with IL-12 and IL-18. Second, most NK cells derived with IL-2 or IL-15 expressed the NK1.1 antigen, while those derived with IL-12 and IL-18 did not. Finally, striking differences were observed regarding cytokine production. Cells stimulated with IL-12 and IL-18 in combination, but not with IL-2 or IL-15, produced IFN-gamma, IL-3, IL-6 and TNF. IFN-gamma was not involved in the response of NK cells to IL-12 and IL-18, as indicated by experiments demonstrating that the combination of the two cytokines displayed similar effects on spleen cells from IFN-gammaR-knock-out mice. Receptor (IL-12Rbeta1, IL-12Rbeta2 and IL-18R) gene expression studies did not indicate that the mechanism underlying the synergy between IL-12 and IL-18 involved reciprocal induction of their receptors. Taken together, our results demonstrate that IL-12 and IL-18 exert striking synergistic activities for NK cell proliferation and activation, distinct from those induced by IL-2 or IL-15.

Animals↗

PubMed1999

Lung fibrosis induced by silica particles in NMRI mice is associated with an upregulation of the p40 subunit of interleukin-12 and Th-2 manifestations.

Interleukin (IL)-12 is a cytokine produced principally by activated macrophages which is involved in control of the T-helper 1/T-helper 2 cell (Th1/Th2) polarization of immune responses. To examine its potential involvement in the development of lung fibrosis, we examined the expression (protein, messenger RNA [mRNA]) of IL-12 (p70) and of its subunits (p40 and p35) in lung homogenates, bronchoalveolar lavage fluid (BALF), and bronchoalveolar lavage (BAL) cell cultures in mouse models of resolutive alveolitis (RA) and fibrosing alveolitis (FA) induced by inorganic particles (manganese dioxide [MnO2] and crystalline silica, respectively). The administration of tungsten carbide (WC), which behaved as an innocuous dust for the lung, served as a negative control condition. The FA was specifically accompanied by a Th2-like polarization characterized by high levels of immunoglobulin (Ig)G1 in BALF and by a protracted overproduction of both p40 protein and mRNA, but not by the biologically active form of IL-12 (p70). In the RA model, the p40 response was only transient, and a Th1-like response was reflected by increased levels of interferon (IFN)-gamma and dominant levels of IgG2a in BALF. Taken together, these findings suggest that production of the p40 subunit of IL-12 and Th2 polarization play important roles in lung inflammatory and fibrotic responses to inhaled inorganic particles.

Animals↗

PubMed1999

Soluble tumor necrosis factor (TNF) receptors p55 and p75 and interleukin-10 downregulate TNF-alpha activity during the lung response to silica particles in NMRI mice.

We have found reduced activity of tumor necrosis factor (TNF)-alpha accompanying resolving and fibrosing alveolitis induced in NMRI mice by mineral particles (MnO2 and SiO2, respectively), which is in apparent contradiction to the well-recognized proinflammatory and profibrotic activities of this cytokine. The objective of this study was to examine the mechanisms involved in this paradoxical response in NMRI mice. Although lung tissue messenger RNA (mRNA) levels for TNF-alpha were transiently (up to 15 d) and persistently (up to 120 d) upregulated in the resolving and fibrosing models, respectively, these changes were not accompanied by a parallel release of TNF-alpha protein, which was respectively transiently and persistently downregulated in bronchoalveolar lavage fluid and bronchoalveolar lavage cell cultures. The downregulation of the TNF-alpha protein was concurrent with the accumulation of recruited polymorphonuclear neutrophils (PMNs) in alveoli, and coculture experiments showed that PMN explanted from the lungs of mice treated with silica particles were able to downregulate the expression of TNF-alpha protein by naive alveolar macrophages. In addition, PMN depletion prevented the downregulation of TNF-alpha induced by silica, further establishing the role of PMNs in the downregulation of TNF-alpha. The possible degradation of TNF-alpha by proteolytic enzymes could be excluded. Marked increases in soluble p55 and p75 TNF receptors (sTNF-R), as well as in interleukin (IL)-10, paralleled the downregulation of TNF-alpha protein. The role of these mediators in the observed reduction of TNF-alpha activity was confirmed by immunoneutralizing the activity of p55 and p75 sTNF-R and by using IL-10-deficient animals. Because IL-10 also exerts profibrotic activity in addition to its antiinflammatory activity, the protracted overproduction of IL-10 observed in fibrosing alveolitis may help the understanding of why, in NMRI mice treated with silica particles, lung fibrosis develops in association with a downregulation of TNF-alpha.

Animals↗

PubMed1999

Ly-6A/E induction by interleukin-6 and interleukin-9 in T cells.

Interleukin-6 (IL-6) is active in the early steps of T cell activation and confers IL-2 responsiveness. In this work, we used EL4 T lymphoma to identify IL-6 target genes in T cells. By differential screening of a cDNA library, we found that IL-6 induced the expression of Ly-6A/E, a GPI-anchored cell surface protein reported to be a regulator of T cell activation. In addition to IL-6, IL-9 and IFN-gamma induced Ly-6A/E expression in EL4 and BW5147 cells. We showed that both IL-6 and IL-9 mediated the transcriptional activation of Ly-6A/E through a GAS element in the Ly-6A/E promoter, which was able to bind STAT1 and STAT3, transcription factors activated by these cytokines. IL-6 had a similar effect in freshly isolated normal T cells, and dramatically increased their proliferation upon Ly-6A/E stimulation. Taken together, our data suggest that Ly-6A/E induction takes part in the T cell activation program initiated by IL-6.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Molecular analysis of human interleukin-9 receptor transcripts in peripheral blood mononuclear cells. Identification of a splice variant encoding for a nonfunctional cell surface receptor.

Genetic studies on mouse models of asthma have identified interleukin-9 (IL9) as a determining factor in controlling bronchial hyperresponsiveness, a hallmark of the disease. Recently, the human IL9 receptor (hIL9R) gene locus has also been implicated in determining susceptibility to bronchial hyperresponsiveness and asthma. In order to evaluate the structure and function of the encoded product, we analyzed receptor transcripts derived from peripheral blood mononuclear cells of 50 unrelated donors. Sequence analysis of the entire coding region identified a splice variant that contains an in frame deletion of a single residue at codon 173 (DeltaQ). This variant could be permanently expressed in a cytokine-dependent murine T-cell line but lacked the ability to induce proliferation in response to human IL9. In situ analyses of cells expressing the wild-type and DeltaQ receptors found both forms to be expressed at the cell surface, but the DeltaQ receptor was unable to bind hIL9 and could not be recognized by N-terminal specific antibodies. These findings demonstrate that hIL9RDeltaQ presents an altered structure and function and suggests its potential role in down-regulating IL9 signaling in effector cells and associated biological processes.

Alternative Splicing↗