Role of CCL19/21 and its possible signaling through CXCR3 in development of metallophillic macrophages in the mouse thymus

• Published in: Histochemistry and cell biology Vol. 135; no. 6; pp. 593 - 601
• Main Authors: Milićević, Novica M., Miljković, Miloš D., Milićević, Živana, Labudović-Borović, Milica, Wang, Xiaoping, Laan, Martti, Peterson, Pärt, Randall, Troy D., Westermann, Jürgen
• Format: Journal Article
• Language: English
• Published: 25-05-2011
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-011-0818-y

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 CCL19/21-deficient thymus, metallophilic macrophages are present in 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 metallophillic 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, CCL19/21and its possible signaling through CXCR3 are required for the development of thymic metallophilic macrophages, whereas the CXCL13-CXCR5 signaling is not necessary.