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Role of Homeostatic Chemokine and Sphingosine‐1‐Phosphate Receptors in the Organization of Lymphoid Tissue
Author(s) -
MÜLLER GERD,
REITERER PHILLIP,
HÖPKEN UTA E.,
GOLFIER SVEN,
LIPP MARTIN
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb06038.x
Subject(s) - c c chemokine receptor type 7 , lymphocyte homing receptor , cxcr5 , ccl21 , lymphocyte , high endothelial venules , chemokine receptor , biology , chemokine , immunology , lymphatic system , cxcl13 , homing (biology) , cc chemokine receptors , c c chemokine receptor type 6 , ccl20 , innate lymphoid cell , microbiology and biotechnology , inflammation , immune system , acquired immune system , cell , cell adhesion , ecology , genetics
A bstract : Chemokines regulate both homeostatic leukocyte recirculation and trafficking to sites of infection and inflammation. Apart from the well‐established physiological functions, chemokines receive growing interest for their role in pathophysiological processes such as autoimmune diseases, cancer, and allograft rejection. The chemokine receptor CCR7, which is responsible for directing T cells, B cells, and dendritic cells (DCs) into secondary lymphoid organs and their precise positioning therein, has already been implicated in lymphoid organ infiltration by neoplastic cells and the localization of metastasis formation. We have shown that the differential expression of CCR7 by neoplastic cells in two entities of Hodgkin's disease (HD), classic HD (cHD) and the nodular lymphocyte predominant HD (NLPHD), may account for the differences observed in tumor cell dissemination within the affected lymph nodes. Because of the prominent role of the chemokine receptors CCR7 and CXCR5 in lymphocyte homing to secondary lymphoid organs, we hypothesized that they may also be involved in the action of FTY720, a synthetic immunosuppressant inducing lymphopenia. By using CXCR5 and CCR7 knockout mice, we have tested for a possible function of these receptors in the FTY720‐induced migration of lymphocytes into Peyer's patches (PPs) and peripheral lymph nodes (PLNs). Lymphopenia is noticeably delayed in mice lacking CCR7, whereas CXCR5 knockout mice show a significant reduction of lymphocyte accumulation in secondary lymphoid organs that are infrequently present in these mice. However, FTY720‐induced lymphocyte sequestration appears to be essentially independent of CCR7 and CXCR5.