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CCR7 deficiency causes ectopic lymphoid neogenesis and disturbed mucosal tissue integrity

Item Type:Article
Title:CCR7 deficiency causes ectopic lymphoid neogenesis and disturbed mucosal tissue integrity
Creators Name:Hoepken, U.E. and Wengner, A.M. and Loddenkemper, C. and Stein, H. and Heimesaat, M.M. and Rehm, A. and Lipp, M.
Abstract:Homeostatic trafficking of lymphocytes through extralymphoid tissues has been recently observed and a potential role in immune surveillance and the establishment of peripheral tolerance is considered. However, the mechanisms regulating lymphocyte recirculation through peripheral tissues under non-inflammatory 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 recirculation of T and B lymphocytes through non-lymphoid 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 topological characteristics of lymph nodes. Flow cytometry analysis of CD4(+) T cells derived from ectopic follicles revealed that CD44(hi)CD62L(lo) effector memory T cells predominate in the gastric lymphoid aggregates. In aged mice, lack of CCR7 induced age-dependent histomorphological changes in the stomach with profound cystic hyperplasia and an increased rate of mucosal proliferation resembling Menetrier's disease. Thus, CCR7 regulates the cellular organization of visceral tissue by governing life-long recirculation of naive and memory lymphocytes under homeostatic conditions.
Keywords:Aging, Cell Proliferation, Leukocyte Chemotaxis, Hypertrophic Gastritis, Hyperplasia, Immunophenotyping, Intestinal Mucosa, Lymphocytes, Knockout Mice, CCR7 Receptors, Chemokine Receptors, Animals, Mice
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:109
Number:3
Page Range:886-895
Date:1 February 2007
Official Publication:https://doi.org/10.1182/blood-2006-03-013532
PubMed:View item in PubMed

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