CCR7 mediates the migration of Foxp3+ regulatory T cells to the paracortical areas of peripheral lymph nodes through high endothelial venules.
Thymus-derived forkhead box p3(+) naturally occurring regulatory T cells (nTreg) are thought to circulate throughout the body to maintain peripheral immunological self-tolerance through interactions with dendritic cells (DCs), resulting in regulation of conventional T cells. However, the chemokine receptors, which are putatively involved in the in vivo migration of nTreg, have not been fully established. Here, we demonstrated that lymph node nTreg preferentially migrated to the paracortical area of lymph nodes after adoptive transfer, where they were observed to make contact frequently with CD8alpha(+) DCs and CD8alpha(-) CD11b(-) DCs. This migration of nTreg to the paracortical areas was impaired severely when cells were prepared from CCR7-deficient mice. However, to some extent, CCR7-independent migration of nTreg in such CCR7-deficient mice was also observed, but this occurred mainly in the medullary high endothelial venules. Taken together, these data provide the evidence that CCR7 mediates nTreg migration to the paracortical areas of lymph nodes under steady-state conditions; however, CCR7-independent migration also takes place in the medulla.
Ueha
Satoshi
S
Department of Molecular Preventive Medicine and SORST, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo, Japan.
Yoneyama
Hiroyuki
H
Hontsu
Shigeto
S
Kurachi
Makoto
M
Kitabatake
Masahiro
M
Abe
Jun
J
Yoshie
Osamu
O
Shibayama
Shiro
S
Sugiyama
Tetsuya
T
Matsushima
Kouji
K
D019264:Adoptive Transfer; D000388:Air; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007700:Kinetics; D008198:Lymph Nodes; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000502:physiology*; D019707:Receptors, Chemokine / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014699:Venules / Q000166:cytology / Q000378:metabolism*
C515355:Ccr4 protein, mouse; C515371:Ccr7 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D019707:Receptors, Chemokine