J. Exp. Med., Volume 187, Number 6, March 16, 1998 939-948

Signal Transducer and Activator of Transcription Factor 6 (Stat6)-deficient Mice Are Protected from Antigen-induced Airway Hyperresponsiveness and Mucus Production

By Douglas Kuperman,^* Brian Schofield,^* Marsha Wills-Karp,^* and Michael J. Grusby^§

From the ^* Department of Environmental Health Sciences, Johns Hopkins School of Public Health, Baltimore, Maryland 21205; and the  Department of Immunology and Infectious Diseases, Harvard School of Public Health, and ^§ Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

The pleiotropic cytokine interleukin 4 (IL-4) has been shown to regulate many processes thought to be important in the allergic diathesis. To determine the mechanism(s) by which IL-4 mediates allergic airway responses to inhaled allergens, we compared the effects of antigen sensitization and challenge on the development of allergic airway responses in mice in which the gene for the signal transducer and activator of transcription factor 6 (Stat6) was disrupted to those of their wild-type littermates. Strikingly, Stat6-deficient mice failed to develop airway hyperresponsiveness (AHR), which was observed in their wild-type littermates after allergen provocation. Moreover, antigen-induced increases in mucus-containing cells were found to be completely Stat6 dependent. Consistent with the lack of Th2 cytokine responses in Stat6-deficient mice, no ovalbumin-specific immunoglobulin (Ig)E was detected in their serum. In contrast, Stat6 signaling only partially mediated antigen-induced eosinophilia with no role in vascular adhesion molecule 1 expression. These results indicate that Stat6 signal transduction is critical in the development of allergen-induced AHR and that agents that specifically inhibit this pathway may provide a novel strategy for the treatment of allergic disorders.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Darcan-Nicolaisen, Y., Meinicke, H., Fels, G., Hegend, O., Haberland, A., Kuhl, A., Loddenkemper, C., Witzenrath, M., Kube, S., Henke, W., Hamelmann, E. (2009). Small Interfering RNA against Transcription Factor STAT6 Inhibits Allergic Airway Inflammation and Hyperreactivity in Mice. J. Immunol. 182: 7501-7508 [Abstract] [Full Text]  
• Fukuyama, S., Nakano, T., Matsumoto, T., Oliver, B. G. G., Burgess, J. K., Moriwaki, A., Tanaka, K., Kubo, M., Hoshino, T., Tanaka, H., McKenzie, A. N. J., Matsumoto, K., Aizawa, H., Nakanishi, Y., Yoshimura, A., Black, J. L., Inoue, H. (2009). Pulmonary Suppressor of Cytokine Signaling-1 Induced by IL-13 Regulates Allergic Asthma Phenotype. Am. J. Respir. Crit. Care Med. 179: 992-998 [Abstract] [Full Text]  
• Gally, F., Hartney, J. M., Janssen, W. J., Perraud, A.-L. (2009). CD38 Plays a Dual Role in Allergen-Induced Airway Hyperresponsiveness. Am. J. Respir. Cell Mol. Bio. 40: 433-442 [Abstract] [Full Text]  
• Wills-Karp, M., Finkelman, F. D. (2008). Untangling the Complex Web of IL-4- and IL-13-Mediated Signaling Pathways. Sci Signal 1: pe55-pe55 [Abstract] [Full Text]  
• Zhou, B., Headley, M. B., Aye, T., Tocker, J., Comeau, M. R., Ziegler, S. F. (2008). Reversal of Thymic Stromal Lymphopoietin-Induced Airway Inflammation through Inhibition of Th2 Responses. J. Immunol. 181: 6557-6562 [Abstract] [Full Text]  
• Moynihan, B., Tolloczko, B., Michoud, M.-C., Tamaoka, M., Ferraro, P., Martin, J. G. (2008). MAP kinases mediate interleukin-13 effects on calcium signaling in human airway smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L171-L177 [Abstract] [Full Text]  
• Xiang, J., Rir-Sim-Ah, J., Tesfaigzi, Y. (2008). IL-9 and IL-13 Induce Mucous Cell Metaplasia That Is Reduced by IFN-{gamma} in a Bax-Mediated Pathway. Am. J. Respir. Cell Mol. Bio. 38: 310-317 [Abstract] [Full Text]  
• King, S. B. S., Knorn, A. M., Ohnmacht, C., Voehringer, D. (2008). Accumulation of Effector CD4 T Cells during Type 2 Immune Responses Is Negatively Regulated by Stat6. J. Immunol. 180: 754-763 [Abstract] [Full Text]  
• Kaplan, M. H., Sehra, S., Chang, H.-C., O'Malley, J. T., Mathur, A. N., Bruns, H. A. (2007). Constitutively active STAT6 predisposes toward a lymphoproliferative disorder. Blood 110: 4367-4369 [Abstract] [Full Text]  
• von Garnier, C., Wikstrom, M. E., Zosky, G., Turner, D. J., Sly, P. D., Smith, M., Thomas, J. A., Judd, S. R., Strickland, D. H., Holt, P. G., Stumbles, P. A. (2007). Allergic Airways Disease Develops after an Increase in Allergen Capture and Processing in the Airway Mucosa. J. Immunol. 179: 5748-5759 [Abstract] [Full Text]  
• Young, H. W. J., Williams, O. W., Chandra, D., Bellinghausen, L. K., Perez, G., Suarez, A., Tuvim, M. J., Roy, M. G., Alexander, S. N., Moghaddam, S. J., Adachi, R., Blackburn, M. R., Dickey, B. F., Evans, C. M. (2007). Central Role of Muc5ac Expression in Mucous Metaplasia and Its Regulation by Conserved 5' Elements. Am. J. Respir. Cell Mol. Bio. 37: 273-290 [Abstract] [Full Text]  
• Johnson, J. R., Swirski, F. K., Gajewska, B. U., Wiley, R. E., Fattouh, R., Pacitto, S. R., Wong, J. K., Stampfli, M. R., Jordana, M. (2007). Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L730-L739 [Abstract] [Full Text]  
• McCusker, C. T., Wang, Y., Shan, J., Kinyanjui, M. W., Villeneuve, A., Michael, H., Fixman, E. D. (2007). Inhibition of Experimental Allergic Airways Disease by Local Application of a Cell-Penetrating Dominant-Negative STAT-6 Peptide. J. Immunol. 179: 2556-2564 [Abstract] [Full Text]  
• Mishra, A., Wang, M., Schlotman, J., Nikolaidis, N. M., DeBrosse, C. W., Karow, M. L., Rothenberg, M. E. (2007). Resistin-like molecule-beta is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L305-L313 [Abstract] [Full Text]  
• Brown, J. P., Taube, C., Miyahara, N., Koya, T., Pelanda, R., Gelfand, E. W., Torres, R. M. (2007). Arhgef1 Is Required by T Cells for the Development of Airway Hyperreactivity and Inflammation. Am. J. Respir. Crit. Care Med. 176: 10-19 [Abstract] [Full Text]  
• Kallinich, T., Beier, K. C., Wahn, U., Stock, P., Hamelmann, E. (2007). T-cell co-stimulatory molecules: their role in allergic immune reactions. Eur Respir J 29: 1246-1255 [Abstract] [Full Text]  
• Steenwinckel, V., Louahed, J., Orabona, C., Huaux, F., Warnier, G., McKenzie, A., Lison, D., Levitt, R., Renauld, J.-C. (2007). IL-13 Mediates In Vivo IL-9 Activities on Lung Epithelial Cells but Not on Hematopoietic Cells. J. Immunol. 178: 3244-3251 [Abstract] [Full Text]  
• Temann, U.-A., Laouar, Y., Eynon, E. E., Homer, R., Flavell, R. A. (2007). IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells. Int Immunol 19: 1-10 [Abstract] [Full Text]  
• Ingram, J. L., Antao-Menezes, A., Mangum, J. B., Lyght, O., Lee, P. J., Elias, J. A., Bonner, J. C. (2006). Opposing Actions of Stat1 and Stat6 on IL-13-Induced Up-Regulation of Early Growth Response-1 and Platelet-Derived Growth Factor Ligands in Pulmonary Fibroblasts. J. Immunol. 177: 4141-4148 [Abstract] [Full Text]  
• Iwashita, H., Morita, S., Sagiya, Y., Nakanishi, A. (2006). Role of Eosinophil Chemotactic Factor by T Lymphocytes on Airway Hyperresponsiveness in a Murine Model of Allergic Asthma. Am. J. Respir. Cell Mol. Bio. 35: 103-109 [Abstract] [Full Text]  
• Rudd, B. D., Smit, J. J., Flavell, R. A., Alexopoulou, L., Schaller, M. A., Gruber, A., Berlin, A. A., Lukacs, N. W. (2006). Deletion of TLR3 Alters the Pulmonary Immune Environment and Mucus Production during Respiratory Syncytial Virus Infection. J. Immunol. 176: 1937-1942 [Abstract] [Full Text]  
• Rose, M. C., Voynow, J. A. (2006). Respiratory Tract Mucin Genes and Mucin Glycoproteins in Health and Disease. Physiol. Rev. 86: 245-278 [Abstract] [Full Text]  
• Georas, S. N., Guo, J., De Fanis, U., Casolaro, V. (2005). T-helper cell type-2 regulation in allergic disease. Eur Respir J 26: 1119-1137 [Abstract] [Full Text]  
• Kuperman, D. A., Huang, X., Nguyenvu, L., Holscher, C., Brombacher, F., Erle, D. J. (2005). IL-4 Receptor Signaling in Clara Cells Is Required for Allergen-Induced Mucus Production. J. Immunol. 175: 3746-3752 [Abstract] [Full Text]  
• Deshpande, D. A., White, T. A., Dogan, S., Walseth, T. F., Panettieri, R. A., Kannan, M. S. (2005). CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle. Am. J. Physiol. Lung Cell. Mol. Physiol. 288: L773-L788 [Abstract] [Full Text]  
• Finkelman, F. D., Yang, M., Perkins, C., Schleifer, K., Sproles, A., Santeliz, J., Bernstein, J. A., Rothenberg, M. E., Morris, S. C., Wills-Karp, M. (2005). Suppressive Effect of IL-4 on IL-13-Induced Genes in Mouse Lung. J. Immunol. 174: 4630-4638 [Abstract] [Full Text]  
• Takatori, H., Nakajima, H., Kagami, S.-i., Hirose, K., Suto, A., Suzuki, K., Kubo, M., Yoshimura, A., Saito, Y., Iwamoto, I. (2005). Stat5a Inhibits IL-12-Induced Th1 Cell Differentiation through the Induction of Suppressor of Cytokine Signaling 3 Expression. J. Immunol. 174: 4105-4112 [Abstract] [Full Text]  
• Takatori, H., Nakajima, H., Hirose, K., Kagami, S.-i., Tamachi, T., Suto, A., Suzuki, K., Saito, Y., Iwamoto, I. (2005). Indispensable Role of Stat5a in Stat6-Independent Th2 Cell Differentiation and Allergic Airway Inflammation. J. Immunol. 174: 3734-3740 [Abstract] [Full Text]  
• Fulkerson, P. C., Zimmermann, N., Hassman, L. M., Finkelman, F. D., Rothenberg, M. E. (2004). Pulmonary Chemokine Expression Is Coordinately Regulated by STAT1, STAT6, and IFN-{gamma}. J. Immunol. 173: 7565-7574 [Abstract] [Full Text]  
• Heller, N. M., Matsukura, S., Georas, S. N., Boothby, M. R., Rothman, P. B., Stellato, C., Schleimer, R. P. (2004). Interferon-{gamma} Inhibits STAT6 Signal Transduction and Gene Expression in Human Airway Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 31: 573-582 [Abstract] [Full Text]  
• Stephenson, L., Johns, M. H., Woodward, E., Mora, A. L., Boothby, M. (2004). An IL-4R{alpha} Allelic Variant, I50, Acts as a Gain-of-Function Variant Relative to V50 for Stat6, But Not Th2 Differentiation. J. Immunol. 173: 4523-4528 [Abstract] [Full Text]  
• Hoshino, A., Tsuji, T., Matsuzaki, J., Jinushi, T., Ashino, S., Teramura, T., Chamoto, K., Tanaka, Y., Asakura, Y., Sakurai, T., Mita, Y., Takaoka, A., Nakaike, S., Takeshima, T., Ikeda, H., Nishimura, T. (2004). STAT6-mediated signaling in Th2-dependent allergic asthma: critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation. Int Immunol 16: 1497-1505 [Abstract] [Full Text]  
• Arimura, A., van Peer, M., Schroder, A. J., Rothman, P. B. (2004). The Transcriptional Co-activator p/CIP (NCoA-3) Is Up-regulated by STAT6 and Serves as a Positive Regulator of Transcriptional Activation by STAT6. J. Biol. Chem. 279: 31105-31112 [Abstract] [Full Text]  
• Deshpande, D. A., Dogan, S., Walseth, T. F., Miller, S. M., Amrani, Y., Panettieri, R. A., Kannan, M. S. (2004). Modulation of Calcium Signaling by Interleukin-13 in Human Airway Smooth Muscle: Role of CD38/Cyclic Adenosine Diphosphate Ribose Pathway. Am. J. Respir. Cell Mol. Bio. 31: 36-42 [Abstract] [Full Text]  
• Kelly-Welch, A. E., Melo, M. E. F., Smith, E., Ford, A. Q., Haudenschild, C., Noben-Trauth, N., Keegan, A. D. (2004). Complex Role of the IL-4 Receptor {alpha} in a Murine Model of Airway Inflammation: Expression of the IL-4 Receptor {alpha} on Nonlymphoid Cells of Bone Marrow Origin Contributes to Severity of Inflammation. J. Immunol. 172: 4545-4555 [Abstract] [Full Text]  
• Blanchard, C., Durual, S., Estienne, M., Bouzakri, K., Heim, M. H., Blin, N., Cuber, J.-C. (2004). IL-4 and IL-13 Up-Regulate Intestinal Trefoil Factor Expression: Requirement for STAT6 and De Novo Protein Synthesis. J. Immunol. 172: 3775-3783 [Abstract] [Full Text]  
• Fulkerson, P. C., Zimmermann, N., Brandt, E. B., Muntel, E. E., Doepker, M. P., Kavanaugh, J. L., Mishra, A., Witte, D. P., Zhang, H., Farber, J. M., Yang, M., Foster, P. S., Rothenberg, M. E. (2004). Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-{gamma} (Mig, CXCL9). Proc. Natl. Acad. Sci. USA 101: 1987-1992 [Abstract] [Full Text]  
• Wan, H., Kaestner, K. H., Ang, S.-L., Ikegami, M., Finkelman, F. D., Stahlman, M. T., Fulkerson, P. C., Rothenberg, M. E., Whitsett, J. A. (2004). Foxa2 regulates alveolarization and goblet cell hyperplasia. Development 131: 953-964 [Abstract] [Full Text]  
• Galietta, L. J. V., Folli, C., Caci, E., Pedemonte, N., Taddei, A., Ravazzolo, R., Zegarra-Moran, O. (2004). Effect of Inflammatory Stimuli on Airway Ion Transport. Proc Am Thorac Soc 1: 62-65 [Abstract] [Full Text]  
• Atherton, H. C., Jones, G., Danahay, H. (2003). IL-13-induced changes in the goblet cell density of human bronchial epithelial cell cultures: MAP kinase and phosphatidylinositol 3-kinase regulation. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L730-L739 [Abstract] [Full Text]  
• Jacob, C. O., Zang, S., Li, L., Ciobanu, V., Quismorio, F., Mizutani, A., Satoh, M., Koss, M. (2003). Pivotal Role of Stat4 and Stat6 in the Pathogenesis of the Lupus-Like Disease in the New Zealand Mixed 2328 Mice. J. Immunol. 171: 1564-1571 [Abstract] [Full Text]  
• Hadeiba, H., Locksley, R. M. (2003). Lung CD25 CD4 Regulatory T Cells Suppress Type 2 Immune Responses But Not Bronchial Hyperreactivity. J. Immunol. 170: 5502-5510 [Abstract] [Full Text]  
• Raman, K., Kaplan, M. H., Hogaboam, C. M., Berlin, A., Lukacs, N. W. (2003). STAT4 Signal Pathways Regulate Inflammation and Airway Physiology Changes in Allergic Airway Inflammation Locally Via Alteration of Chemokines. J. Immunol. 170: 3859-3865 [Abstract] [Full Text]  
• Ingram, J. L., Rice, A., Geisenhoffer, K., Madtes, D. K., Bonner, J. C. (2003). Interleukin-13 Stimulates the Proliferation of Lung Myofibroblasts via a Signal Transducer and Activator of Transcription-6-Dependent Mechanism: A Possible Mechanism for the Development of Airway Fibrosis in Asthma. Chest 123: 422S-424S [Full Text]  
• Stutz, A. M., Pickart, L. A., Trifilieff, A., Baumruker, T., Prieschl-Strassmayr, E., Woisetschlager, M. (2003). The Th2 Cell Cytokines IL-4 and IL-13 Regulate Found in Inflammatory Zone 1/Resistin-Like Molecule {alpha} Gene Expression by a STAT6 and CCAAT/Enhancer-Binding Protein-Dependent Mechanism. J. Immunol. 170: 1789-1796 [Abstract] [Full Text]  
• Kondo, M., Tamaoki, J., Takeyama, K., Nakata, J., Nagai, A. (2002). Interleukin-13 Induces Goblet Cell Differentiation in Primary Cell Culture from Guinea Pig Tracheal Epithelium. Am. J. Respir. Cell Mol. Bio. 27: 536-541 [Abstract] [Full Text]  
• Welch, J. S., Escoubet-Lozach, L., Sykes, D. B., Liddiard, K., Greaves, D. R., Glass, C. K. (2002). TH2 Cytokines and Allergic Challenge Induce Ym1 Expression in Macrophages by a STAT6-dependent Mechanism. J. Biol. Chem. 277: 42821-42829 [Abstract] [Full Text]  
• Chang, H.-C., Zhang, S., Kaplan, M. H. (2002). Neonatal Tolerance in the Absence of Stat4- and Stat6- Dependent Th Cell Differentiation. J. Immunol. 169: 4124-4128 [Abstract] [Full Text]  
• Ritz, S. A., Cundall, M. J., Gajewska, B. U., Alvarez, D., Gutierrez-Ramos, J.-C., Coyle, A. J., McKenzie, A. N. J., Stampfli, M. R., Jordana, M. (2002). Granulocyte Macrophage Colony-Stimulating Factor-Driven Respiratory Mucosal Sensitization Induces Th2 Differentiation and Function Independently of Interleukin-4. Am. J. Respir. Cell Mol. Bio. 27: 428-435 [Abstract] [Full Text]  
• Kumar, R. K., Foster, P. S. (2002). Modeling Allergic Asthma in Mice: Pitfalls and Opportunities. Am. J. Respir. Cell Mol. Bio. 27: 267-272 [Abstract] [Full Text]  
• Duetsch, G., Illig, T., Loesgen, S., Rohde, K., Klopp, N., Herbon, N., Gohlke, H., Altmueller, J., Wjst, M. (2002). STAT6 as an asthma candidate gene: polymorphism-screening, association and haplotype analysis in a Caucasian sib-pair study. Hum Mol Genet 11: 613-621 [Abstract] [Full Text]  
• Venkayya, R., Lam, M., Willkom, M., Grunig, G., Corry, D. B., Erle, D. J. (2002). The Th2 Lymphocyte Products IL-4 and IL-13 Rapidly Induce Airway Hyperresponsiveness Through Direct Effects on Resident Airway Cells. Am. J. Respir. Cell Mol. Bio. 26: 202-208 [Abstract] [Full Text]  
• Blease, K., Schuh, J. M., Jakubzick, C., Lukacs, N. W., Kunkel, S. L., Joshi, B. H., Puri, R. K., Kaplan, M. H., Hogaboam, C. M. (2002). Stat6-Deficient Mice Develop Airway Hyperresponsiveness and Peribronchial Fibrosis during Chronic Fungal Asthma. Am. J. Pathol. 160: 481-490 [Abstract] [Full Text]  
• Perez-G., M., Melo, M., Keegan, A. D., Zamorano, J. (2002). Aspirin and Salicylates Inhibit the IL-4- and IL-13-Induced Activation of STAT6. J. Immunol. 168: 1428-1434 [Abstract] [Full Text]  
• Galietta, L. J. V., Pagesy, P., Folli, C., Caci, E., Romio, L., Costes, B., Nicolis, E., Cabrini, G., Goossens, M., Ravazzolo, R., Zegarra-Moran, O. (2002). IL-4 Is a Potent Modulator of Ion Transport in the Human Bronchial Epithelium In Vitro. J. Immunol. 168: 839-845 [Abstract] [Full Text]  
• Singer, M., Lefort, J., Vargaftig, B. B. (2002). Granulocyte Depletion and Dexamethasone Differentially Modulate Airways Hyperreactivity, Inflammation, Mucus Accumulation, and Secretion Induced by rmIL-13 or Antigen. Am. J. Respir. Cell Mol. Bio. 26: 74-84 [Abstract] [Full Text]  
• FAHY, J. V. (2001). Remodeling of the Airway Epithelium in Asthma. Am. J. Respir. Crit. Care Med. 164: S46-51 [Abstract] [Full Text]  
• Lee, J. H., Kaminski, N., Dolganov, G., Grunig, G., Koth, L., Solomon, C., Erle, D. J., Sheppard, D. (2001). Interleukin-13 Induces Dramatically Different Transcriptional Programs in Three Human Airway Cell Types. Am. J. Respir. Cell Mol. Bio. 25: 474-485 [Abstract] [Full Text]  
• Hoeck, J., Woisetschlager, M. (2001). Activation of Eotaxin-3/CCL26 Gene Expression in Human Dermal Fibroblasts Is Mediated by STAT6. J. Immunol. 167: 3216-3222 [Abstract] [Full Text]  
• Wu, C. A., Puddington, L., Whiteley, H. E., Yiamouyiannis, C. A., Schramm, C. M., Mohammadu, F., Thrall, R. S. (2001). Murine Cytomegalovirus Infection Alters Th1/Th2 Cytokine Expression, Decreases Airway Eosinophilia, and Enhances Mucus Production in Allergic Airway Disease. J. Immunol. 167: 2798-2807 [Abstract] [Full Text]  
• Mattes, J., Yang, M., Siqueira, A., Clark, K., MacKenzie, J., McKenzie, A. N. J., Webb, D. C., Matthaei, K. I., Foster, P. S. (2001). IL-13 Induces Airways Hyperreactivity Independently of the IL-4R{alpha} Chain in the Allergic Lung. J. Immunol. 167: 1683-1692 [Abstract] [Full Text]  
• Kips, J.C. (2001). Cytokines in asthma. Eur Respir J 18: 24S-33s [Abstract] [Full Text]  
• Mathew, A., MacLean, J. A., DeHaan, E., Tager, A. M., Green, F. H.Y., Luster, A. D. (2001). Signal Transducer and Activator of Transcription 6 Controls Chemokine Production and T Helper Cell Type 2 Cell Trafficking in Allergic Pulmonary Inflammation. JEM 193: 1087-1096 [Abstract] [Full Text]  
• Russo, M., Nahori, M.-A., Lefort, J., Gomes, E., de Castro Keller, A., Rodriguez, D., Ribeiro, O. G., Adriouch, S., Gallois, V., de Faria, A. M. C., Vargaftig, B. B. (2001). Suppression of Asthma-like Responses in Different Mouse Strains by Oral Tolerance. Am. J. Respir. Cell Mol. Bio. 24: 518-526 [Abstract] [Full Text]  
• Tomkinson, A., Duez, C., Cieslewicz, G., Pratt, J. C., Joetham, A., Shanafelt, M.-C., Gundel, R., Gelfand, E. W. (2001). A Murine IL-4 Receptor Antagonist That Inhibits IL-4- and IL-13-Induced Responses Prevents Antigen-Induced Airway Eosinophilia and Airway Hyperresponsiveness. J. Immunol. 166: 5792-5800 [Abstract] [Full Text]  
• Kim, Y., Sung, S.-s. J., Kuziel, W. A., Feldman, S., Fu, S. M., Rose, C. E. Jr (2001). Enhanced Airway Th2 Response After Allergen Challenge in Mice Deficient in CC Chemokine Receptor-2 (CCR2). J. Immunol. 166: 5183-5192 [Abstract] [Full Text]  
• Hoeck, J., Woisetschlager, M. (2001). STAT6 Mediates Eotaxin-1 Expression in IL-4 or TNF-{{alpha}}-Induced Fibroblasts. J. Immunol. 166: 4507-4515 [Abstract] [Full Text]  
• Matsukawa, A., Kaplan, M. H., Hogaboam, C. M., Lukacs, N. W., Kunkel, S. L. (2001). Pivotal Role of Signal Transducer and Activator of Transcription (Stat)4 and Stat6 in the Innate Immune Response during Sepsis. JEM 193: 679-688 [Abstract] [Full Text]  
• Kips, J.C., Tournoy, K.G., Pauwels, R.A. (2001). New anti-asthma therapies: suppression of the effect of interleukin (IL)-4 and IL-5. Eur Respir J 17: 499-506 [Abstract] [Full Text]  
• Tekkanat, K. K., Maassab, H. F., Cho, D. S., Lai, J. J., John, A., Berlin, A., Kaplan, M. H., Lukacs, N. W. (2001). IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent. J. Immunol. 166: 3542-3548 [Abstract] [Full Text]  
• Shim, J. J., Dabbagh, K., Ueki, I. F., Dao-Pick, T., Burgel, P.-R., Takeyama, K., Tam, D. C.-W., Nadel, J. A. (2001). IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L134-L140 [Abstract] [Full Text]  
• Ostrand-Rosenberg, S., Grusby, M. J., Clements, V. K. (2000). Cutting Edge: STAT6-Deficient Mice Have Enhanced Tumor Immunity to Primary and Metastatic Mammary Carcinoma. J. Immunol. 165: 6015-6019 [Abstract] [Full Text]  
• Kacha, A. K., Fallarino, F., Markiewicz, M. A., Gajewski, T. F. (2000). Spontaneous Rejection of Poorly Immunogenic P1.HTR Tumors by Stat6-Deficient Mice. J. Immunol. 165: 6024-6028 [Abstract] [Full Text]  
• Deng, J., Yeung, V. P., Tsitoura, D., DeKruyff, R. H., Umetsu, D. T., Levy, S. (2000). Allergen-Induced Airway Hyperreactivity Is Diminished in CD81-Deficient Mice. J. Immunol. 165: 5054-5061 [Abstract] [Full Text]  
• KIPS, J. C., TOURNOY, K. G., PAUWELS, R. A. (2000). Gene Knockout Models of Asthma. Am. J. Respir. Crit. Care Med. 162: S66-70 [Full Text]  
• Venkataraman, C., Schaefer, G., Schindler, U. (2000). Cutting Edge: Chandra, a Novel Four-Transmembrane Domain Protein Differentially Expressed in Helper Type 1 Lymphocytes. J. Immunol. 165: 632-636 [Abstract] [Full Text]  
• Zhang, S., Lukacs, N. W., Lawless, V. A., Kunkel, S. L., Kaplan, M. H. (2000). Cutting Edge: Differential Expression of Chemokines in Th1 and Th2 Cells Is Dependent on Stat6 But Not Stat4. J. Immunol. 165: 10-14 [Abstract] [Full Text]  
• Webb, D. C., McKenzie, A. N. J., Koskinen, A. M. L., Yang, M., Mattes, J., Foster, P. S. (2000). Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity. J. Immunol. 165: 108-113 [Abstract] [Full Text]  
• Wills-Karp, M. (2000). Trophic Slime, Allergic Slime. Am. J. Respir. Cell Mol. Bio. 22: 637-639 [Full Text]  
• Hadeiba, H., Corry, D. B., Locksley, R. M. (2000). Baseline Airway Hyperreactivity in A/J Mice Is not Mediated by Cells of the Adaptive Immune System. J. Immunol. 164: 4933-4940 [Abstract] [Full Text]  
• Koglin, J., Glysing-Jensen, T., Gadiraju, S., Russell, M. E. (2000). Attenuated Cardiac Allograft Vasculopathy in Mice With Targeted Deletion of the Transcription Factor STAT4. Circulation 101: 1034-1039 [Abstract] [Full Text]  
• Zuhdi Alimam, M., Piazza, F. M., Selby, D. M., Letwin, N., Huang, L., Rose, M. C. (2000). Muc-5/5ac Mucin Messenger RNA and Protein Expression Is a Marker of Goblet Cell Metaplasia in Murine Airways. Am. J. Respir. Cell Mol. Bio. 22: 253-260 [Abstract] [Full Text]  
• Kagami, S.-i., Nakajima, H., Kumano, K., Suzuki, K., Suto, A., Imada, K., Davey, H. W., Saito, Y., Takatsu, K., Leonard, W. J., Iwamoto, I. (2000). Both Stat5a and Stat5b are required for antigen-induced eosinophil and T-cell recruitment into the tissue. Blood 95: 1370-1377 [Abstract] [Full Text]  
• Matsukura, S., Stellato, C., Plitt, J. R., Bickel, C., Miura, K., Georas, S. N., Casolaro, V., Schleimer, R. P. (1999). Activation of Eotaxin Gene Transcription by NF-{kappa}B and STAT6 in Human Airway Epithelial Cells. J. Immunol. 163: 6876-6883 [Abstract] [Full Text]  
• Hill, S., Herlaar, E., Le Cardinal, A., van Heeke, G., Nicklin, P. (1999). Homologous Human and Murine Antisense Oligonucleotides Targeting Stat6 . Functional Effects on Germline Cepsilon Transcript. Am. J. Respir. Cell Mol. Bio. 21: 728-737 [Abstract] [Full Text]  
• TOMKINSON, A., KANEHIRO, A., RABINOVITCH, N., JOETHAM, A., CIESLEWICZ, G., GELFAND, E. W. (1999). The Failure of STAT6-deficient Mice to Develop Airway Eosinophilia and Airway Hyperresponsiveness Is Overcome by Interleukin-5. Am. J. Respir. Crit. Care Med. 160: 1283-1291 [Abstract] [Full Text]  
• Dickensheets, H. L., Venkataraman, C., Schindler, U., Donnelly, R. P. (1999). Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression. Proc. Natl. Acad. Sci. USA 96: 10800-10805 [Abstract] [Full Text]  
• Chin, J. E., Hatfield, C. A., Winterrowd, G. E., Krzesicki, R. F., Shull, K. L., Fidler, S. F., Kolbasa, K. P., Brashler, J. R., Griffin, R. L., Fleming, W. E., Justen, J. M., Banitt, L. S., Bundy, G. L., Richards, I. M. (1999). Preclinical Evaluation of Anti-inflammatory Activities of the Novel Pyrrolopyrimidine PNU-142731A, a Potential Treatment for Asthma. J. Pharmacol. Exp. Ther. 290: 188-195 [Abstract] [Full Text]  
• Kato, Y., Manabe, T., Tanaka, Y., Mochizuki, H. (1999). Effect of an Orally Active Th1/Th2 Balance Modulator, M50367, on IgE Production, Eosinophilia, and Airway Hyperresponsiveness in Mice. J. Immunol. 162: 7470-7479 [Abstract] [Full Text]  
• Levings, M. K., Bessette, D. C., Schrader, J. W. (1999). Interleukin-4 Synergizes With Raf-1 to Promote Long-Term Proliferation and Activation of c-jun N-terminal Kinase. Blood 93: 3694-3702 [Abstract] [Full Text]  
• Cohn, L., Homer, R. J., MacLeod, H., Mohrs, M., Brombacher, F., Bottomly, K. (1999). Th2-Induced Airway Mucus Production Is Dependent on IL-4R{alpha}, But Not on Eosinophils. J. Immunol. 162: 6178-6183 [Abstract] [Full Text]  
• Dabbagh, K., Takeyama, K., Lee, H.-M., Ueki, I. F., Lausier, J. A., Nadel, J. A. (1999). IL-4 Induces Mucin Gene Expression and Goblet Cell Metaplasia In Vitro and In Vivo. J. Immunol. 162: 6233-6237 [Abstract] [Full Text]  
• Akira, S. (1999). Functional Roles of STAT Family Proteins: Lessons from Knockout Mice. Stem Cells 17: 138-146 [Abstract] [Full Text]  
• Levings, M. K., Schrader, J. W. (1999). IL-4 Inhibits the Production of TNF-{alpha} and IL-12 by STAT6-Dependent and -Independent Mechanisms. J. Immunol. 162: 5224-5229 [Abstract] [Full Text]  
• Wills-Karp, M., Luyimbazi, J., Xu, X., Schofield, B., Neben, T. Y., Karp, C. L., Donaldson, D. D. (1998). Interleukin-13: Central Mediator of Allergic Asthma. Science 282: 2258-2261 [Abstract] [Full Text]  
• Dent, A. L., Hu-Li, J., Paul, W. E., Staudt, L. M. (1998). T helper type 2 inflammatory disease in the absence of interleukin 4 and transcription factor STAT6. Proc. Natl. Acad. Sci. USA 95: 13823-13828 [Abstract] [Full Text]  
• Cohn, L., Tepper, J. S., Bottomly, K. (1998). Cutting Edge: IL-4-Independent Induction of Airway Hyperresponsiveness by Th2, But Not Th1, Cells. J. Immunol. 161: 3813-3816 [Abstract] [Full Text]  
• Daniel, C., Salvekar, A., Schindler, U. (2000). A Gain-of-function Mutation in STAT6. J. Biol. Chem. 275: 14255-14259 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS