Role of CCL19/21 and its possible signaling through CXCR3 in development of metallophilic macrophages in the mouse thymus |
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Authors: | Novica M Mili?evi? Milo? D Miljkovi? ?ivana Mili?evi? Milica Labudovi?-Borovi? Xiaoping Wang Martti Laan Pärt Peterson Troy D Randall Jürgen Westermann |
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Institution: | 1.Institute of Histology and Embryology, Faculty of Medicine,University of Belgrade,Belgrade,Serbia;2.Molecular Pathology, Institute of General and Molecular Pathology,Tartu University,Tartu,Estonia;3.Division of Allergy Immunology and Rheumatology, Department of Medicine,University of Rochester,Rochester,USA;4.Center for Structural and Cell Biology in Medicine,Institute of Anatomy, University of Lübeck,Lübeck,Germany |
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Abstract: | We have already shown that metallophilic macrophages, which represent an important component in the thymus physiology, are
lacking in lymphotoxin-β receptor-deficient mice. However, further molecular requirements for the development and correct
tissue positioning of these cells are unknown. To this end, we studied a panel of mice deficient in different chemokine ligand
or receptor genes. In contrast to normal mice, which have these cells localized in the thymic cortico-medullary zone (CMZ)
as a distinct row positioned between the cortex and medulla, in plt/plt (paucity of lymph node T cells) mice lacking the functional
CCL19/CCL21 chemokines, metallophilic macrophages are not present in the thymic tissue. Interestingly, in contrast to the
CCL19/21-deficient thymus, metallophilic macrophages are present in the CCR7-deficient thymus. However, these cells are not
appropriately located in the CMZ, but are mostly crowded in central parts of thymic medulla. The double staining revealed
that these metallophilic macrophages are CCR7-negative and CXCR3-positive. In the CXCL13-deficient thymus the number, morphology
and localization of metallophilic macrophages are normal. Thus, our study shows that CCL19/21 and its possible signaling through
CXCR3 are required for the development of thymic metallophilic macrophages, whereas the CXCL13–CXCR5 signaling is not necessary. |
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