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https://hdl.handle.net/2440/57684
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Type: | Journal article |
Title: | Autoimmune regulator deficiency results in decreased expression of CCR4 and CCR7 ligands and in delayed migration of CD4⁺ Thymocytes |
Other Titles: | Autoimmune regulator deficiency results in decreased expression of CCR4 and CCR7 ligands and in delayed migration of CD4(+) thymocytes |
Author: | Laan, M. Kisand, K. Kont, V. Moll, K. Tserel, L. Scott, H. Peterson, P. |
Citation: | Journal of Immunology, 2009; 183(12):7682-7691 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2009 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | Martti Laan, Kai Kisand, Vivian Kont, Kaidi Möll, Liina Tserel, Hamish S. Scott, and Pärt Peterson |
Abstract: | Autoimmune regulator (Aire) has been viewed as a central player in the induction of tolerance. This study examines whether Aire can modulate the production of the thymic chemokines involved in corticomedullary migration and thus play a role in intrathymic thymocyte migration and maturation. Aire deficiency resulted in reduced gene expression and protein levels of the CCR4 and CCR7 ligands in whole thymi of mice, as determined by quantitative PCR analysis and ELISA. The expression of the CCR4 ligands coincided with Aire expression in the CD80(high) medullary thymic epithelial cells, whereas the expression of the CCR7 ligands was detected in other cell populations. Also, the expression pattern of the CCR4 and CCR7 ligands follows that of Aire during postnatal but not during embryonic development. In vitro, overexpression of Aire resulted in an up-regulation of selected CCR4 and CCR7 ligands, which induced selective migration of double-positive and single-positive CD4(+) cells. In vivo, Aire deficiency resulted in a diminished emigration of mature CD4(+) T cells from the thymi of 5-day-old mice. In conclusion, Aire regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes. These results suggest a novel mechanism behind the Aire-dependent induction of central tolerance. |
Keywords: | Thymus Gland CD4-Positive T-Lymphocytes Cell Line Epithelial Cells Animals Mice, Inbred C57BL Mice, Knockout Mice Transcription Factors Ligands Cell Migration Inhibition Cell Differentiation Down-Regulation Receptors, CCR4 Receptors, CCR7 AIRE Protein |
Rights: | Copyright © 2009 by The American Association of Immunologists, Inc. |
DOI: | 10.4049/jimmunol.0804133 |
Published version: | http://dx.doi.org/10.4049/jimmunol.0804133 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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