Aberrant In Vivo T Helper Type 2 Cell Response and Impaired Eosinophil Recruitment in CC Chemokine Receptor 8 Knockout Mice

doi:10.1084/jem.193.5.573

Published online 26 February 2001.

This Article

	Full Text
	Full Text (PDF, 495K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Chensue, S. W.
	Articles by Lira, S. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Chensue, S. W.
	Articles by Lira, S. A.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/2001/3/573/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 5, March 5, 2001 573-584

Original Article

Aberrant In Vivo T Helper Type 2 Cell Response and Impaired Eosinophil Recruitment in CC Chemokine Receptor 8 Knockout Mice

Stephen W. Chensue^a, Nicholas W. Lukacs^a, Tong-Yuan Yang^f, Xiaozhou Shang^a, Kirsten A. Frait^a, Steven L. Kunkel^a, Ted Kung^f, Maria T. Wiekowski^f, Joseph A. Hedrick^d, Donald N. Cook^f, Alessandra Zingoni^b, Satwant K. Narula^f, Albert Zlotnik^e, Franck J. Barrat^e, Anne O'Garra^e, Monica Napolitano^c, and Sergio A. Lira^f
^a Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48105
^b Department of Experimental Medicine and Pathology, University of Rome, 00167 Rome, Italy
^c Instituto Dermopatico dell'Immacolata-IRCCS, 00167 Rome, Italy
^d Human Genome Research, Palo Alto, California 94304
^e DNAX Research Institute for Cellular and Molecular Biology, Palo Alto, California 94304
^f Department of Immunology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033

Correspondence to: Sergio A. Lira, Department of Immunology K15 D-210C, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033-0539. Tel:908-740-3088 Fax:908-740-3084 E-mail:sergio.lira{at}spcorp.com.

Chemokine receptors transduce signals important for the functionand trafficking of leukocytes. Recently, it has been shown thatCC chemokine receptor (CCR)8 is selectively expressed by Th2subsets, but its functional relevance is unclear. To addressthe biological role of CCR8, we generated CCR8 deficient (-/-)mice. Here we report defective T helper type 2 (Th2) immuneresponses in vivo in CCR8^-/- mice in models of Schistosoma mansonisoluble egg antigen (SEA)-induced granuloma formation as wellas ovalbumin (OVA)- and cockroach antigen (CRA)-induced allergicairway inflammation. In these mice, the response to SEA, OVA,and CRA showed impaired Th2 cytokine production that was associatedwith aberrant type 2 inflammation displaying a 50 to 80% reductionin eosinophils. In contrast, a prototypical Th1 immune response,elicited by Mycobacteria bovis purified protein derivative (PPD)was unaffected by CCR8 deficiency. Mechanistic analyses indicatedthat Th2 cells developed normally and that the reduction ineosinophil recruitment was likely due to systemic reductionin interleukin 5. These results indicate an important role forCCR8 in Th2 functional responses in vivo.

Key Words: chemokine receptors, chemokines, T helper type 2 cells, allergy,granulomas

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

This article has been cited by other articles:

Mira, E., Leon, B., Barber, D. F., Jimenez-Baranda, S., Goya, I., Almonacid, L., Marquez, G., Zaballos, A., Martinez-A., C., Stein, J. V., Ardavin, C., Manes, S. (2008). Statins Induce Regulatory T Cell Recruitment via a CCL1 Dependent Pathway. J. Immunol. 181: 3524-3534 [Abstract] [Full Text]
Szameit, S., Vierlinger, K., Farmer, L., Tuschl, H., Noehammer, C. (2008). Microarray-Based In Vitro Test System for the Discrimination of Contact Allergens and Irritants: Identification of Potential Marker Genes. Clin. Chem. 54: 525-533 [Abstract] [Full Text]
Cantor, J., Haskins, K. (2007). Recruitment and Activation of Macrophages by Pathogenic CD4 T Cells in Type 1 Diabetes: Evidence for Involvement of CCR8 and CCL1. J. Immunol. 179: 5760-5767 [Abstract] [Full Text]
Gonzalo, J.-A., Qiu, Y., Lora, J. M., Al-Garawi, A., Villeval, J.-L., Boyce, J. A., Martinez-A, C., Marquez, G., Goya, I., Hamid, Q., Fraser, C. C., Picarella, D., Cote-Sierra, J., Hodge, M. R., Gutierrez-Ramos, J.-C., Kolbeck, R., Coyle, A. J. (2007). Coordinated Involvement of Mast Cells and T Cells in Allergic Mucosal Inflammation: Critical Role of the CC Chemokine Ligand 1:CCR8 Axis. J. Immunol. 179: 1740-1750 [Abstract] [Full Text]
Jensen, P. C., Nygaard, R., Thiele, S., Elder, A., Zhu, G., Kolbeck, R., Ghosh, S., Schwartz, T. W., Rosenkilde, M. M. (2007). Molecular Interaction of a Potent Nonpeptide Agonist with the Chemokine Receptor CCR8. Mol. Pharmacol. 72: 327-340 [Abstract] [Full Text]
Fox, J. M., Najarro, P., Smith, G. L., Struyf, S., Proost, P., Pease, J. E. (2006). Structure/Function Relationships of CCR8 Agonists and Antagonists: AMINO-TERMINAL EXTENSION OF CCL1 BY A SINGLE AMINO ACID GENERATES A PARTIAL AGONIST. J. Biol. Chem. 281: 36652-36661 [Abstract] [Full Text]
Freeman, C. M., Stolberg, V. R., Chiu, B.-C., Lukacs, N. W., Kunkel, S. L., Chensue, S. W. (2006). CCR4 Participation in Th Type 1 (Mycobacterial) and Th Type 2 (Schistosomal) Anamnestic Pulmonary Granulomatous Responses. J. Immunol. 177: 4149-4158 [Abstract] [Full Text]
Sironi, M., Martinez, F. O., D'Ambrosio, D., Gattorno, M., Polentarutti, N., Locati, M., Gregorio, A., Iellem, A., Cassatella, M. A., Van Damme, J., Sozzani, S., Martini, A., Sinigaglia, F., Vecchi, A., Mantovani, A. (2006). Differential regulation of chemokine production by Fc{gamma} receptor engagement in human monocytes: association of CCL1 with a distinct form of M2 monocyte activation (M2b, Type 2). J. Leukoc. Biol. 80: 342-349 [Abstract] [Full Text]
Montes-Vizuet, R., Vega-Miranda, A., Valencia-Maqueda, E., Negrete-Garcia, M. C., Velasquez, J. R., Teran, L. M. (2006). CC chemokine ligand 1 is released into the airways of atopic asthmatics. Eur Respir J 28: 59-67 [Abstract] [Full Text]
Suto, H., Nakae, S., Kakurai, M., Sedgwick, J. D., Tsai, M., Galli, S. J. (2006). Mast Cell-Associated TNF Promotes Dendritic Cell Migration. J. Immunol. 176: 4102-4112 [Abstract] [Full Text]
Haskell, C. A., Horuk, R., Liang, M., Rosser, M., Dunning, L., Islam, I., Kremer, L., Gutierrez, J., Marquez, G., Martinez-A, C., Biscone, M. J., Doms, R. W., Ribeiro, S. (2006). Identification and Characterization of a Potent, Selective Nonpeptide Agonist of the CC Chemokine Receptor CCR8. Mol. Pharmacol. 69: 309-316 [Abstract] [Full Text]
Carpenter, K. J., Hogaboam, C. M. (2005). Immunosuppressive Effects of CCL17 on Pulmonary Antifungal Responses during Pulmonary Invasive Aspergillosis. Infect. Immun. 73: 7198-7207 [Abstract] [Full Text]
Martin, P., Villares, R., Rodriguez-Mascarenhas, S., Zaballos, A., Leitges, M., Kovac, J., Sizing, I., Rennert, P., Marquez, G., Martinez-A, C., Diaz-Meco, M. T., Moscat, J. (2005). Control of T helper 2 cell function and allergic airway inflammation by PKC{zeta}. Proc. Natl. Acad. Sci. USA 102: 9866-9871 [Abstract] [Full Text]
Souza, A. L. S., Roffe, E., Pinho, V., Souza, D. G., Silva, A. F., Russo, R. C., Guabiraba, R., Pereira, C. A. J., Carvalho, F. M., Barsante, M. M., Correa-Oliveira, R., Fraga, L. A. O., Negrao-Correa, D., Teixeira, M. M. (2005). Potential Role of the Chemokine Macrophage Inflammatory Protein 1{alpha} in Human and Experimental Schistosomiasis. Infect. Immun. 73: 2515-2523 [Abstract] [Full Text]
Kleinewietfeld, M., Puentes, F., Borsellino, G., Battistini, L., Rotzschke, O., Falk, K. (2005). CCR6 expression defines regulatory effector/memory-like cells within the CD25+CD4+ T-cell subset. Blood 105: 2877-2886 [Abstract] [Full Text]
Matthews, S. P., Tregoning, J. S., Coyle, A. J., Hussell, T., Openshaw, P. J. M. (2005). Role of CCL11 in Eosinophilic Lung Disease during Respiratory Syncytial Virus Infection. J. Virol. 79: 2050-2057 [Abstract] [Full Text]
Freeman, C. M., Chiu, B.-C., Stolberg, V. R., Hu, J., Zeibecoglou, K., Lukacs, N. W., Lira, S. A., Kunkel, S. L., Chensue, S. W. (2005). CCR8 Is Expressed by Antigen-Elicited, IL-10-Producing CD4+CD25+ T Cells, Which Regulate Th2-Mediated Granuloma Formation in Mice. J. Immunol. 174: 1962-1970 [Abstract] [Full Text]
Puneet, P., Moochhala, S., Bhatia, M. (2005). Chemokines in acute respiratory distress syndrome. Am. J. Physiol. Lung Cell. Mol. Physiol. 288: L3-L15 [Abstract] [Full Text]
Poynter, M. E., Cloots, R., van Woerkom, T., Butnor, K. J., Vacek, P., Taatjes, D. J., Irvin, C. G., Janssen-Heininger, Y. M. W. (2004). NF-{kappa}B Activation in Airways Modulates Allergic Inflammation but Not Hyperresponsiveness. J. Immunol. 173: 7003-7009 [Abstract] [Full Text]
Qu, C., Edwards, E. W., Tacke, F., Angeli, V., Llodra, J., Sanchez-Schmitz, G., Garin, A., Haque, N. S., Peters, W., van Rooijen, N., Sanchez-Torres, C., Bromberg, J., Charo, I. F., Jung, S., Lira, S. A., Randolph, G. J. (2004). Role of CCR8 and Other Chemokine Pathways in the Migration of Monocyte-derived Dendritic Cells to Lymph Nodes. JEM 200: 1231-1241 [Abstract] [Full Text]
Gutierrez, J., Kremer, L., Zaballos, A., Goya, I., Martinez-A., C., Marquez, G. (2004). Analysis of Post-translational CCR8 Modifications and Their Influence on Receptor Activity. J. Biol. Chem. 279: 14726-14733 [Abstract] [Full Text]
Oostendorp, J., Hylkema, M. N., Luinge, M., Geerlings, M., Meurs, H., Timens, W., Zaagsma, J., Postma, D. S., Boddeke, H. W., Biber, K. (2004). Localization and Enhanced mRNA Expression of the Orphan Chemokine Receptor L-CCR in the Lung in a Murine Model of Ovalbumin-induced Airway Inflammation. J. Histochem. Cytochem. 52: 401-410 [Abstract] [Full Text]
Gyetko, M. R., Sud, S., Chensue, S. W. (2004). Urokinase-Deficient Mice Fail To Generate a Type 2 Immune Response following Schistosomal Antigen Challenge. Infect. Immun. 72: 461-467 [Abstract] [Full Text]
Najarro, P., Lee, H.-J., Fox, J., Pease, J., Smith, G. L. (2003). Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1. J. Gen. Virol. 84: 3325-3336 [Abstract] [Full Text]
Conroy, D. M., Jopling, L. A., Lloyd, C. M., Hodge, M. R., Andrew, D. P., Williams, T. J., Pease, J. E., Sabroe, I. (2003). CCR4 blockade does not inhibit allergic airways inflammation. J. Leukoc. Biol. 74: 558-563 [Abstract] [Full Text]
Honda, K., Arima, M., Cheng, G., Taki, S., Hirata, H., Eda, F., Fukushima, F., Yamaguchi, B., Hatano, M., Tokuhisa, T., Fukuda, T. (2003). Prostaglandin D2 Reinforces Th2 Type Inflammatory Responses of Airways to Low-dose Antigen through Bronchial Expression of Macrophage-derived Chemokine. JEM 198: 533-543 [Abstract] [Full Text]
Lippert, E., Yowe, D. L., Gonzalo, J.-A., Justice, J. P., Webster, J. M., Fedyk, E. R., Hodge, M., Miller, C., Gutierrez-Ramos, J.-C., Borrego, F., Keane-Myers, A., Druey, K. M. (2003). Role of Regulator of G Protein Signaling 16 in Inflammation- Induced T Lymphocyte Migration and Activation. J. Immunol. 171: 1542-1555 [Abstract] [Full Text]
Lukacs, N. W., Miller, A. L., Hogaboam, C. M. (2003). Chemokine Receptors in Asthma: Searching for the Correct Immune Targets. J. Immunol. 171: 11-15 [Full Text]
Mueller, C., August, A. (2003). Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK. J. Immunol. 170: 5056-5063 [Abstract] [Full Text]
Bishop, B., Lloyd, C. M. (2003). CC Chemokine Ligand 1 Promotes Recruitment of Eosinophils But Not Th2 Cells During the Development of Allergic Airways Disease. J. Immunol. 170: 4810-4817 [Abstract] [Full Text]
DeVries, M. E., Cao, H., Wang, J., Xu, L., Kelvin, A. A., Ran, L., Chau, L. A., Madrenas, J., Hegele, R. A., Kelvin, D. J. (2003). Genomic Organization and Evolution of the CX3CR1/CCR8 Chemokine Receptor Locus. J. Biol. Chem. 278: 11985-11994 [Abstract] [Full Text]
Goya, I., Villares, R., Zaballos, A., Gutierrez, J., Kremer, L., Gonzalo, J.-A., Varona, R., Carramolino, L., Serrano, A., Pallares, P., Criado, L. M., Kolbeck, R., Torres, M., Coyle, A. J., Gutierrez-Ramos, J.-C., Martinez-A, C., Marquez, G. (2003). Absence of CCR8 Does Not Impair the Response to Ovalbumin-Induced Allergic Airway Disease. J. Immunol. 170: 2138-2146 [Abstract] [Full Text]
Trebst, C., Staugaitis, S. M., Kivisakk, P., Mahad, D., Cathcart, M. K., Tucky, B., Wei, T., Rani, M. R. S., Horuk, R., Aldape, K. D., Pardo, C. A., Lucchinetti, C. F., Lassmann, H., Ransohoff, R. M. (2003). CC Chemokine Receptor 8 in the Central Nervous System Is Associated with Phagocytic Macrophages. Am. J. Pathol. 162: 427-438 [Abstract] [Full Text]
Spinetti, G., Bernardini, G., Camarda, G., Mangoni, A., Santoni, A., Capogrossi, M. C., Napolitano, M. (2003). The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway. J. Leukoc. Biol. 73: 201-207 [Abstract] [Full Text]
Chung, C. D., Kuo, F., Kumer, J., Motani, A. S., Lawrence, C. E., Henderson, W. R. Jr., Venkataraman, C. (2003). CCR8 Is Not Essential for the Development of Inflammation in a Mouse Model of Allergic Airway Disease. J. Immunol. 170: 581-587 [Abstract] [Full Text]
Murphy, C. A., Hoek, R. M., Wiekowski, M. T., Lira, S. A., Sedgwick, J. D. (2002). Interactions Between Hemopoietically Derived TNF and Central Nervous System-Resident Glial Chemokines Underlie Initiation of Autoimmune Inflammation in the Brain. J. Immunol. 169: 7054-7062 [Abstract] [Full Text]
Metwali, A., Blum, A., Elliott, D. E., Weinstock, J. V. (2002). Interleukin-4 Receptor {alpha} Chain and STAT6 Signaling Inhibit Gamma Interferon but Not Th2 Cytokine Expression within Schistosome Granulomas. Infect. Immun. 70: 5651-5658 [Abstract] [Full Text]
Randolph, G. J., Sanchez-Schmitz, G., Liebman, R. M., Schakel, K. (2002). The CD16+ (Fc{gamma}RIII+) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting. JEM 196: 517-527 [Abstract] [Full Text]
Lukacs, N. W., John, A., Berlin, A., Bullard, D. C., Knibbs, R., Stoolman, L. M. (2002). E- and P-Selectins Are Essential for the Development of Cockroach Allergen-Induced Airway Responses. J. Immunol. 169: 2120-2125 [Abstract] [Full Text]
Chiu, B.-C., Shang, X.-Z., Stolberg, V. R., Komuniecki, E., Chensue, S. W. (2002). Population analysis of CD4+ T cell chemokine receptor transcript expression during in vivo type-1 (mycobacterial) and type-2 (schistosomal) immune responses. J. Leukoc. Biol. 72: 363-372 [Abstract] [Full Text]
Mathew, A., Medoff, B. D., Carafone, A. D., Luster, A. D. (2002). Cutting Edge: Th2 Cell Trafficking into the Allergic Lung Is Dependent on Chemoattractant Receptor Signaling. J. Immunol. 169: 651-655 [Abstract] [Full Text]
Vicentini, L., Mazzi, P., Caveggion, E., Continolo, S., Fumagalli, L., Lapinet-Vera, J. A., Lowell, C. A., Berton, G. (2002). Fgr Deficiency Results in Defective Eosinophil Recruitment to the Lung During Allergic Airway Inflammation. J. Immunol. 168: 6446-6454 [Abstract] [Full Text]
Oliveira, S. H. P., Lira, S., Martinez-A, C., Wiekowski, M., Sullivan, L., Lukacs, N. W. (2002). Increased responsiveness of murine eosinophils to MIP-1{beta} (CCL4) and TCA-3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8. J. Leukoc. Biol. 71: 1019-1025 [Abstract] [Full Text]
Lukacs, N. W., Berlin, A., Schols, D., Skerlj, R. T., Bridger, G. J. (2002). AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity. Am. J. Pathol. 160: 1353-1360 [Abstract] [Full Text]
Sabroe, I., Lloyd, C.M., Whyte, M.K.B., Dower, S.K., Williams, T.J., Pease, J.E. (2002). Chemokines, innate and adaptive immunity, and respiratory disease. Eur Respir J 19: 350-355 [Abstract] [Full Text]
Heydtmann, M, Adams, D H (2002). Understanding selective trafficking of lymphocyte subsets. Gut 50: 150-152 [Full Text]
Park, M. K., Hoffmann, K. F., Cheever, A. W., Amichay, D., Wynn, T. A., Farber, J. M. (2001). Patterns of Chemokine Expression in Models of Schistosoma mansoni Inflammation and Infection Reveal Relationships between Type 1 and Type 2 Responses and Chemokines In Vivo. Infect. Immun. 69: 6755-6768 [Abstract] [Full Text]
D'AMBROSIO, D., MARIANI, M., PANINA-BORDIGNON, P., SINIGAGLIA, F. (2001). Chemokines and Their Receptors Guiding T Lymphocyte Recruitment in Lung Inflammation. Am. J. Respir. Crit. Care Med. 164: 1266-1275 [Full Text]