IL-13 Mediates In Vivo IL-9 Activities on Lung Epithelial Cells but Not on Hematopoietic Cells

Steenwinckel, Valérie; Louahed, Jamila; Orabona, Ciriana; Huaux, François; Warnier, Guy; McKenzie, Andrew N. J.; Lison, Dominique; Levitt, Roy C.; Renauld, Jean Christophe

doi:10.4049/jimmunol.178.5.3244

Cited by 91 publications

(70 citation statements)

References 55 publications

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“…IL-9R Ϫ/Ϫ mice were generated in the C57BL/6 background by deletion of the exons 2-6 of the IL-9R␣-chain, corresponding to the extracellular part of the receptor as described in Ref. 5. For the current study, IL-9R Ϫ/Ϫ mice were backcrossed for five generations onto BALB/c background.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that Retnla was induced by IL-9 in an IL-13-dependent way in lungs (5). We therefore analyzed the colonic expression of Retnla in our model.…”

Section: Pla2g4c and Resistin-like ␣ But Not Paneth Cell Markers Armentioning

confidence: 99%

“…Indeed, IL-9 transgenic (Tg) 3 and IL-13 Tg mice show increased mucus production by lung goblet cells (1,2) and airway hyperresponsiveness (2)(3)(4). Further studies of IL-9 Tg mice showed that IL-9 activities on lung epithelial cells are actually mediated by up-regulation of IL-13 expression by T and mast cells (5)(6)(7).…”

mentioning

confidence: 99%

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IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

Steenwinckel

Louahed²,

Lemaire³

et al. 2009

The Journal of Immunology

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IL-9 contributes to lung inflammatory processes such as asthma, by promoting mast cell differentiation, B cell activation, eosinophilia, and mucus production by lung epithelial cells. The observation that IL-9 overexpressing mice show increased mast cell numbers in the intestinal mucosa suggests that this cytokine might also play a role in intestinal inflammation. In colons from IL-9 transgenic mice, the expression of Muc2, a major intestinal mucin gene, was up-regulated, together with that of CLCA3 chloride channel and resistin like α, which are goblet cell-associated genes. Additional IL-9 up-regulated genes were identified and included innate immunity genes such as angiogenin 4 and the PLA2g2a phospholipase A2, which are typical Paneth cell markers. Histochemical staining of Paneth cells by phloxine/tartrazine showed that IL-9 induces Paneth cell hyperplasia in Lieberkühn glands of the small intestine, and in the colonic mucosa, where this cell type is normally absent. Expression of Paneth cell markers, including angiogenin 4, PLA2g2a, and cryptdins, was induced in the colon of wild-type mice after two to four daily administrations of IL-9. By crossing IL-9 transgenic mice with IL-13−/− mice, or by injecting IL-9 into IL-4R−/− mice, we showed that IL-13 was required for the up-regulation of these Paneth cell-specific genes by IL-9. Taken together, our data indicate that Paneth cell hyperplasia and expression of their various antimicrobial products contribute to the immune response driven by TH2 cytokines, such as IL-9 and IL-13 in the intestinal mucosa.

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Section: Methodsmentioning

confidence: 99%

“…We have previously shown that Retnla was induced by IL-9 in an IL-13-dependent way in lungs (5). We therefore analyzed the colonic expression of Retnla in our model.…”

Section: Pla2g4c and Resistin-like ␣ But Not Paneth Cell Markers Armentioning

confidence: 99%

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IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

Steenwinckel

Louahed²,

Lemaire³

et al. 2009

The Journal of Immunology

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“…Asthmatic patients show increased expression of IL-9 and its receptor in the airways (19). Many of the effects of IL-9 in mice (eosinophilic inflammation and mucus hypersecretion) are mediated via the release of IL-13, whereas its effects on mast cell expansion and B cells seem to be direct (20). IL-9 plays an important role in differentiation and proliferation of mast cells and interacts synergistically with SCF.…”

Section: Figurementioning

confidence: 99%

The cytokine network in asthma and chronic obstructive pulmonary disease

Barnes¹

2008

J. Clin. Invest.

828

714

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Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases. IntroductionThe most common inflammatory diseases of the airways are asthma and chronic obstructive pulmonary disease (COPD), and the incidence of both is increasing throughout the world. The prevalence of asthma in developed countries is approximately 10% in adults and even higher in children, whereas in developing countries, the prevalence is lower but increasing rapidly. The global prevalence of COPD is approximately 10% among individuals over the age of 40 years. Asthma often starts in early childhood and is characterized by intermittent wheezing and shortness of breath. In contrast, the predominant symptom in COPD is shortness of breath on exertion, which is persistent and slowly progressive. Although the clinical symptoms of both diseases are caused by airway narrowing as a result of inflammation in the airways, there are marked differences in the patterns of underlying inflammation.Cytokines play a key role in orchestrating the chronic inflammation of asthma and COPD by recruiting, activating, and promoting the survival of multiple inflammatory cells in the respiratory tract (Figure 1, Figure 2, and Table 1). Over 50 cytokines have now been identified in asthma and COPD, but their role in the pathophysiology of these complex airway diseases is often unclear. For the purpose of this Review, cytokines are classified into lymphokines (cytokines that are secreted by T cells and regulate immune responses), proinflammatory cytokines (cytokines that amplify and perpetuate the inflammatory process), growth factors (cytokines that promote cell survival and result in structural changes in the airways), chemokines (cytokines that are chemotactic for inflammatory cells), and antiinflammatory cytokines (cytokines that negatively modulate the inflammatory response), although many of these functions may overlap. Where possible, I have focused on human studies and have emphasized any therapeutic interventions that have been made.

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“…Swiss mice were obtained from Janvier (Elevage Janvier, Le GenestSt-Isle, France). As previously described, 36 IL-9R KO mice were obtained in the C57BL6 background by replacing a 2.8-kb genomic KpnI-SpeI fragment containing exons 2-6 by a neomycin resistance gene, leading to a complete loss of the extracellular binding domain.…”

Section: Kdamentioning

confidence: 99%

IL-9/IL-9 receptor signaling selectively protects cortical neurons against developmental apoptosis

et al. 2008

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In mammals, programmed cell death (PCD) is a central event during brain development. Trophic factors have been shown to prevent PCD in postmitotic neurons. Similarly, cytokines have neurotrophic effects involving regulation of neuronal survival. Nevertheless, neuronal PCD is only partially understood and host determinants are incompletely defined. The present study provides evidence that the cytokine interleukin-9 (IL-9) and its receptor specifically control PCD of neurons in the murine newborn neocortex. IL-9 antiapoptotic action appeared to be time-restricted to early postnatal stages as both ligand and receptor transcripts were mostly expressed in neocortex between postnatal days 0 and 10. This period corresponds to the physiological peak of apoptosis for postmitotic neurons in mouse neocortex. In vivo studies showed that IL-9/IL-9 receptor pathway inhibits apoptosis in the newborn neocortex. Furthermore, in vitro studies demonstrated that IL-9 and its receptor are mainly expressed in neurons. IL-9 effects were mediated by the activation of the JAK/STAT (janus kinase/signal transducer and activator of transcription) pathway, whereas nuclear factor-jB (NF-jB) or Erk pathways were not involved in mediating IL-9-induced inhibition of cell death. Finally, IL-9 reduced the expression of the mitochondrial pro-apoptotic factor Bax whereas Bcl-2 level was not significantly affected. Together, these data suggest that IL-9/IL-9 receptor signaling pathway represents a novel endogenous antiapoptotic mechanism for cortical neurons by controlling JAK/STAT and Bax levels.

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IL-13 Mediates In Vivo IL-9 Activities on Lung Epithelial Cells but Not on Hematopoietic Cells

Cited by 91 publications

References 55 publications

IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

IL-9 Promotes IL-13-Dependent Paneth Cell Hyperplasia and Up-Regulation of Innate Immunity Mediators in Intestinal Mucosa

The cytokine network in asthma and chronic obstructive pulmonary disease

IL-9/IL-9 receptor signaling selectively protects cortical neurons against developmental apoptosis

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