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Essential role of CCL21 in establishment of central self-tolerance in T cells.

  • Kozai M Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, Japan.
  • Kubo Y Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, Japan.
  • Katakai T Department of Immunology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
  • Kondo H Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, Japan.
  • Kiyonari H Animal Resource Development Unit and Genetic Engineering Team, Institute of Physical and Chemical Research Center for Life Science Technologies, Kobe, Japan.
  • Schaeuble K Department of Biochemistry, Center for Immunity and Infection, University of Lausanne, Lausanne, Switzerland.
  • Luther SA Department of Biochemistry, Center for Immunity and Infection, University of Lausanne, Lausanne, Switzerland.
  • Ishimaru N Division of Molecular Pathology, Graduate School of Oral Sciences, University of Tokushima, Tokushima, Japan.
  • Ohigashi I Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, Japan takahama@genome.tokushima-u.ac.jp ohigashi@genome.tokushima-u.ac.jp.
  • Takahama Y Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, Japan takahama@genome.tokushima-u.ac.jp ohigashi@genome.tokushima-u.ac.jp.
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  • 2017-06-15
Published in:
  • The Journal of experimental medicine. - 2017
Animals
Autoimmune Diseases
Central Tolerance
Chemokine CCL21
Dacryocystitis
Flow Cytometry
Gene Expression
Lymph Nodes
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Mice, Transgenic
Microscopy, Confocal
Receptors, CCR7
Reverse Transcriptase Polymerase Chain Reaction
Self Tolerance
T-Lymphocytes
Thymocytes
Thymus Gland
English The chemokine receptor CCR7 directs T cell relocation into and within lymphoid organs, including the migration of developing thymocytes into the thymic medulla. However, how three functional CCR7 ligands in mouse, CCL19, CCL21Ser, and CCL21Leu, divide their roles in immune organs is unclear. By producing mice specifically deficient in CCL21Ser, we show that CCL21Ser is essential for the accumulation of positively selected thymocytes in the thymic medulla. CCL21Ser-deficient mice were impaired in the medullary deletion of self-reactive thymocytes and developed autoimmune dacryoadenitis. T cell accumulation in the lymph nodes was also defective. These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo.
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  • English
Open access status
hybrid
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https://sonar.ch/global/documents/150687
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