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Blood, 1 February 2007, Vol. 109, No. 3, pp. 886-895. Prepublished online as a Blood First Edition Paper on October 3, 2006; DOI 10.1182/blood-2006-03-013532. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-03-013532v1 109/3/886    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Höpken, U. E. Articles by Lipp, M. Search for Related Content PubMed PubMed Citation Articles by Höpken, U. E. Articles by Lipp, M. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS CCR7 deficiency causes ectopic lymphoid neogenesis and disturbed mucosal tissue integrity Uta E. Höpken1, Antje M. Wengner1, Christoph Loddenkemper2, Harald Stein2, Markus M. Heimesaat3, Armin Rehm4,5, and Martin Lipp1 1 Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; 2 Department of Pathology, Consultation and Reference Center for Lymph Node Pathology and Haematopathology, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany; 3 Department of Medical Microbiology and Immunology of Infection, Charité-Universitätsmedizin Berlin, Germany; 4 Department of Hematology, Oncology, and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; 5 Robert-Rössle-Clinic, Charité-Universitätsmedizin Berlin, Germany Homeostatic trafficking of lymphocytes through extralymphoid tissues has been recently observed, and a potential role in immune surveillance and the establishment of peripheral tolerance are considered. However, the mechanisms regulating lymphocyte recirculation through peripheral tissues under noninflammatory conditions are not well understood. Here, we demonstrate that the chemokine receptor CCR7 controls not only lymphocyte trafficking to and within secondary lymphoid organs but also homeostatic migration of T and B lymphocytes through nonlymphoid tissues. Lack of CCR7 results in a massive accumulation of lymphocytes in epithelial tissues. In particular, the gastrointestinal mucosal tissue of CCR7–/– mice is highly permissive for the formation of lymphoid aggregates, which develop into ectopic follicular structures with major topologic characteristics of lymph nodes. Flow cytometry analysis of CD4+ T cells derived from ectopic follicles revealed that CD44hiCD62Llo effector memory T cells predominate in the gastric lymphoid aggregates. In aged mice, lack of CCR7 induced age-dependent histomorphologic changes in the stomach with profound cystic hyperplasia and an increased rate of mucosal proliferation resembling Menetrier disease. Thus, CCR7 regulates the cellular organization of visceral tissue by governing life-long recirculation of naive and memory lymphocytes under homeostatic conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. P. Martin, T. Marinkovic, C. Canasto-Chibuque, R. Latif, J. C. Unkeless, T. F. Davies, Y. Takahama, G. C. Furtado, and S. A. Lira CCR7 Deficiency in NOD Mice Leads to Thyroiditis and Primary Hypothyroidism J. Immunol., September 1, 2009; 183(5): 3073 - 3080. [Abstract] [Full Text] [PDF] A. H. Achtman, U. E. Hopken, C. Bernert, and M. Lipp CCR7-deficient mice develop atypically persistent germinal centers in response to thymus-independent type 2 antigens J. Leukoc. Biol., March 1, 2009; 85(3): 409 - 417. [Abstract] [Full Text] [PDF] S. Ueha, H. Yoneyama, S. Hontsu, M. Kurachi, M. Kitabatake, J. Abe, O. Yoshie, S. Shibayama, T. Sugiyama, and K. Matsushima CCR7 mediates the migration of Foxp3+ regulatory T cells to the paracortical areas of peripheral lymph nodes through high endothelial venules J. Leukoc. Biol., November 1, 2007; 82(5): 1230 - 1238. [Abstract] [Full Text] [PDF] M. A. Schneider, J. G. Meingassner, M. Lipp, H. D. Moore, and A. Rot CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells J. Exp. Med., April 16, 2007; 204(4): 735 - 745. [Abstract] [Full Text] [PDF]

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