C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE.
Interleukin 17-producing T helper cells (T(H)-17 cells) are important in experimental autoimmune encephalomyelitis, but their route of entry into the central nervous system (CNS) and their contribution relative to that of other effector T cells remain to be determined. Here we found that mice lacking CCR6, a chemokine receptor characteristic of T(H)-17 cells, developed T(H)-17 responses but were highly resistant to the induction of experimental autoimmune encephalomyelitis. Disease susceptibility was reconstituted by transfer of wild-type T cells that entered into the CNS before disease onset and triggered massive CCR6-independent recruitment of effector T cells across activated parenchymal vessels. The CCR6 ligand CCL20 was constitutively expressed in epithelial cells of choroid plexus in mice and humans. Our results identify distinct molecular requirements and ports of lymphocyte entry into uninflamed versus inflamed CNS and suggest that the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS.
Reboldi
Andrea
A
Institute for Research in Biomedicine, Bellinzona, Switzerland.
Coisne
Caroline
C
Baumjohann
Dirk
D
Benvenuto
Federica
F
Bottinelli
Denise
D
Lira
Sergio
S
Uccelli
Antonio
A
Lanzavecchia
Antonio
A
Engelhardt
Britta
B
Sallusto
Federica
F
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D054418:Chemokine CCL20; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002831:Choroid Plexus / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007157:Immunologic Surveillance; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D020381:Interleukin-17; D054399:Receptors, CCR6