TY - JOUR
T1 - Role of CCL19/21 and its possible signaling through CXCR3 in development of metallophilic macrophages in the mouse thymus
AU - Milićević, Novica M.
AU - Miljković, Miloš D.
AU - Milićević, Živana
AU - Labudović-Borović, Milica
AU - Wang, Xiaoping
AU - Laan, Martti
AU - Peterson, Pärt
AU - Randall, Troy D.
AU - Westermann, Jürgen
N1 - Funding Information:
Acknowledgments Thanks are due to Jovanka Ognjanović and Lidija Gutjahr for technical assistance. This work was supported by the Ministry for Science and Technological Development of Republic of Serbia (grant no. 175005) and represents a part of the Institutional Academic Cooperation between Beograd and Lübeck (project DEU/ 1033146), which is financially supported by the Alexander von Humboldt-Foundation, Bonn, Germany. Martti Laan was supported by Estonian Science Foundation (grant no. 8710) and Troy D. Randall by NIH grant HL69409.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960262468&partnerID=8YFLogxK
U2 - 10.1007/s00418-011-0818-y
DO - 10.1007/s00418-011-0818-y
M3 - Journal articles
C2 - 21611855
AN - SCOPUS:79960262468
SN - 0948-6143
VL - 135
SP - 593
EP - 601
JO - Histochemistry and Cell Biology
JF - Histochemistry and Cell Biology
IS - 6
ER -