CCR7 deficiency exacerbates injury in acute nephritis due to aberrant localization of regulatory T cells.
The homing of dendritic cells and T cells to secondary lymphoid organs requires chemokine receptor 7 (CCR7) expression on these cells. T cells mediate the pathogenesis of experimental accelerated nephrotoxic serum nephritis (NTS), including its suppression by regulatory T cells (Tregs), but the contribution of CCR7 to this disease is unknown. Here, we compared the development of NTS in CCR7-knockout (KO) and wild-type (WT) mice. Compared with WT mice, CCR7KO mice developed more severe disease with significantly more inflammatory cells infiltrating the kidney. These cells included FoxP3(+) Tregs, which were virtually absent from WT kidneys. The adoptive transfer of WT Tregs into CCR7KO mice at the time of immunization protected the recipients from disease; these cells homed to secondary lymphoid organs but not to kidneys. Conversely, adoptive transfer of CCR7KO Tregs into WT mice did not inhibit development of NTS. These data suggest that NTS can develop without CCR7 expression, but Treg-mediated disease suppression, which seems to occur in secondary lymphoid organs, requires CCR7.
Eller
Kathrin
K
Innsbruck Medical University, Clinical Division of Internal Medicine IV-Nephrology and Hypertension, Anichstrasse. 35, 6020 Innsbruck, Austria.
Weber
Tobias
T
Pruenster
Monika
M
Wolf
Anna M
AM
Mayer
Gert
G
Rosenkranz
Alexander R
AR
Rot
Antal
A
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D007107:Immune System / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009393:Nephritis / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000473:pathology* / Q000502:physiology*
C515371:Ccr7 protein, mouse; D016207:Cytokines; D054400:Receptors, CCR7