Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/50629
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Type: Journal article
Title: Metallophilic macrophages are fully developed in the thymus of autoimmune regulator (Aire)-deficient mice
Author: Milcevic, N.
Milicevic, Z.
Milkovic, M.
Labudovic-Borovic, M.
Laan, M.
Peterson, P.
Kisand, K.
Scott, H.
Qu, N.
Westermann, J.
Citation: Histochemistry and Cell Biology, 2009; 131(5):643-649
Publisher: Springer-Verlag
Issue Date: 2009
ISSN: 0948-6143
1432-119X
Statement of
Responsibility: 
Novica M. Milićević, Živana Milićević, Miloš D. Miljković, Milica Labudović-Borović, Martti Laan, Pärt Peterson, Kai Kisand, Hamish S. Scott, Ning Qu and Jürgen Westermann
Abstract: Thymic metallophilic macrophages represent a significant component in the thymus physiology. Recently, we showed their presence to be dependent on functional lymphotoxin-beta receptor (LT beta R) signaling pathway. However, it is unknown whether the development of metallophilic macrophages also requires the Autoimmune regulator (Aire) transcription factor, as suggested by some studies for medullary thymic epithelial cells, or perhaps the presence of Aire-expressing thymic epithelial cells themselves. Therefore, we investigated the presence of metallophilic macrophages in Aire-deficient thymus. Our study shows that the metallophilic macrophages are fully developed in the Aire-deficient thymus; their development is not regulated via Aire transcription factor and does not require the presence of Aire-expressing epithelial cells. On the contrary, in alymphoplasia (ALY) mice (deficient in nuclear factor-kappaB-inducing kinase, NIK), which we used as negative control, thymic metallophilic macrophages are completely lacking, similarly as in LT beta R-deficient animals. Together, these results show that the development/maintenance of thymic metallophilic macrophages is executed via LT beta R circumventing the Aire transcription factor. Thus, we shed a new light on the molecular requirements for development of these cells and also show that LT beta R pathway is a common developmental regulator of metallophilic macrophages in different lymphatic organs (i.e., thymus and spleen).
Keywords: Thymus Gland; Macrophages; Animals; Mice, Inbred C57BL; Mice, Knockout; Mice; Protein-Serine-Threonine Kinases; Transcription Factors; Lymphotoxin beta Receptor
Description: Copyright © Springer-Verlag 2009 Thymic metallophilic macrophages represent a significant component in the thymus physiology. Recently, we showed their presence to be dependent on functional lymphotoxin-β receptor (LTβR) signaling pathway. However, it is unknown whether the development of metallophilic macrophages also requires the Autoimmune regulator (Aire) transcription factor, as suggested by some studies for medullary thymic epithelial cells, or perhaps the presence of Aire-expressing thymic epithelial cells themselves. Therefore, we investigated the presence of metallophilic macrophages in Aire-deficient thymus. Our study shows that the metallophilic macrophages are fully developed in the Aire-deficient thymus; their development is not regulated via Aire transcription factor and does not require the presence of Aire-expressing epithelial cells. On the contrary, in alymphoplasia (ALY) mice (deficient in nuclear factor-kappaB-inducing kinase, NIK), which we used as negative control, thymic metallophilic macrophages are completely lacking, similarly as in LTβR-deficient animals. Together, these results show that the development/maintenance of thymic metallophilic macrophages is executed via LTβR circumventing the Aire transcription factor. Thus, we shed a new light on the molecular requirements for development of these cells and also show that LTβR pathway is a common developmental regulator of metallophilic macrophages in different lymphatic organs (i.e., thymus and spleen).
RMID: 0020090451
DOI: 10.1007/s00418-008-0553-1
Appears in Collections:Pathology publications

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